@article {12707, title = {Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning.}, journal = {Molecular Psychiatry}, year = {2022}, abstract = {

Understanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke (N = 53,637). We identified novel loci in the intronic region of CDH18, and at 13q21 and 3p21.1, as well as an expected signal in the APOE/APOC1/TOMM40 region. These results replicated in an independent sample. Functional and bioinformatic analyses supported many of these loci and further implicated POC1. We showed that polygenic score for verbal learning associated with brain activation in right parieto-occipital region during working memory task. Finally, we showed genetic correlations of these memory traits with several neurocognitive and health outcomes. Our findings suggest a role of several genomic loci in verbal memory processes.

}, keywords = {Genome, health outcomes, Memory, neurocognitive outcomes, polygenic score, Verbal Learning}, issn = {1476-5578}, doi = {10.1038/s41380-022-01710-8}, author = {Lahti, Jari and Tuominen, Samuli and Yang, Qiong and Pergola, Giulio and Ahmad, Shahzad and Amin, Najaf and Armstrong, Nicola J and Beiser, Alexa and Bey, Katharina and Bis, Joshua C and Boerwinkle, Eric and Bressler, Jan and Campbell, Archie and Campbell, Harry and Chen, Qiang and Corley, Janie and Cox, Simon R and Davies, Gail and De Jager, Philip L and Derks, Eske M and Jessica Faul and Fitzpatrick, Annette L and Fohner, Alison E and Ford, Ian and Fornage, Myriam and Gerring, Zachary and Grabe, Hans J and Grodstein, Francine and Gudnason, Vilmundur and Simonsick, Eleanor and Holliday, Elizabeth G and Joshi, Peter K and Kajantie, Eero and Kaprio, Jaakko and Karell, Pauliina and Kleineidam, Luca and Knol, Maria J and Kochan, Nicole A and Kwok, John B and Leber, Markus and Lam, Max and Lee, Teresa and Li, Shuo and Loukola, Anu and Luck, Tobias and Marioni, Riccardo E and Mather, Karen A and Medland, Sarah and Mirza, Saira S and Nalls, Mike A and Nho, Kwangsik and O{\textquoteright}Donnell, Adrienne and Oldmeadow, Christopher and Painter, Jodie and Pattie, Alison and Reppermund, Simone and Risacher, Shannon L and Rose, Richard J and Sadashivaiah, Vijay and Scholz, Markus and Satizabal, Claudia L and Schofield, Peter W and Schraut, Katharina E and Scott, Rodney J and Simino, Jeannette and Smith, Albert V and Smith, Jennifer A and Stott, David J and Surakka, Ida and Teumer, Alexander and Thalamuthu, Anbupalam and Trompet, Stella and Turner, Stephen T and van der Lee, Sven J and Villringer, Arno and V{\"o}lker, Uwe and Wilson, Robert S and Wittfeld, Katharina and Vuoksimaa, Eero and Xia, Rui and Yaffe, Kristine and Yu, Lei and Zare, Habil and Zhao, Wei and Ames, David and Attia, John and Bennett, David A and Brodaty, Henry and Chasman, Daniel I and Goldman, Aaron L and Hayward, Caroline and Ikram, M Arfan and Jukema, J Wouter and Sharon L R Kardia and Lencz, Todd and Loeffler, Markus and Mattay, Venkata S and Palotie, Aarno and Psaty, Bruce M and Ramirez, Alfredo and Ridker, Paul M and Riedel-Heller, Steffi G and Sachdev, Perminder S and Saykin, Andrew J and Scherer, Martin and Schofield, Peter R and Sidney, Stephen and Starr, John M and Trollor, Julian and Ulrich, William and Wagner, Michael and David R Weir and Wilson, James F and Wright, Margaret J and Weinberger, Daniel R and Debette, St{\'e}phanie and Eriksson, Johan G and Mosley, Thomas H and Launer, Lenore J and van Duijn, Cornelia M and Deary, Ian J and Seshadri, Sudha and R{\"a}ikk{\"o}nen, Katri} } @article {12132, title = {Genomics of 1 million parent lifespans implicates novel pathways and common diseases and distinguishes survival chances.}, journal = {Elife}, volume = {8}, year = {2019}, pages = {e39856}, abstract = {

We use a genome-wide association of 1 million parental lifespans of genotyped subjects and data on mortality risk factors to validate previously unreplicated findings near , , , , , and 13q21.31, and identify and replicate novel findings near , , and . We also validate previous findings near 5q33.3/ and , whilst finding contradictory evidence at other loci. Gene set and cell-specific analyses show that expression in foetal brain cells and adult dorsolateral prefrontal cortex is enriched for lifespan variation, as are gene pathways involving lipid proteins and homeostasis, vesicle-mediated transport, and synaptic function. Individual genetic variants that increase dementia, cardiovascular disease, and lung cancer - but not other cancers - explain the most variance. Resulting polygenic scores show a mean lifespan difference of around five years of life across the deciles.

Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor{\textquoteright}s assessment is that all the issues have been addressed (see decision letter).

}, keywords = {Age Factors, Aged, Bayes Theorem, Disease, DNA Methylation, Female, Genetic Loci, Genome-Wide Association Study, Genomics, Humans, Longevity, Male, Middle Aged, Multifactorial Inheritance, Parents, Polymorphism, Single Nucleotide, Risk Factors, Sex Characteristics, Signal Transduction, Survival Analysis}, issn = {2050-084X}, doi = {10.7554/eLife.39856}, author = {Paul Rhj Timmers and Mounier, Ninon and Lall, Kristi and Fischer, Krista and Ning, Zheng and Feng, Xiao and Bretherick, Andrew D and Clark, David W and Shen, Xia and T{\~o}nu Esko and Kutalik, Zolt{\'a}n and James F Wilson and Joshi, Peter K} } @article {12123, title = {New alcohol-related genes suggest shared genetic mechanisms with neuropsychiatric disorders.}, journal = {Nature Human Behaviour}, volume = {3}, year = {2019}, pages = {950-961}, abstract = {

Excessive alcohol consumption is one of the main causes of death and disability worldwide. Alcohol consumption is a heritable complex trait. Here we conducted a meta-analysis of genome-wide association studies of alcohol consumption (g d) from the UK Biobank, the Alcohol Genome-Wide Consortium and the Cohorts for Heart and Aging Research in Genomic Epidemiology Plus consortia, collecting data from 480,842 people of European descent to decipher the genetic architecture of alcohol intake. We identified 46 new common loci and investigated their potential functional importance using magnetic resonance imaging data and gene expression studies. We identify genetic pathways associated with alcohol consumption and suggest genetic mechanisms that are shared with neuropsychiatric disorders such as schizophrenia.

}, keywords = {Adult, Aged, Alcohol Drinking, Alcoholism, Brain, Female, genes, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Magnetic Resonance Imaging, Male, Mental Disorders, Middle Aged, Neuroimaging, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Schizophrenia, Whites}, issn = {2397-3374}, doi = {10.1038/s41562-019-0653-z}, author = {Evangelou, Evangelos and Gao, He and Chu, Congying and Ntritsos, Georgios and Blakeley, Paul and Butts, Andrew R and Pazoki, Raha and Suzuki, Hideaki and Koskeridis, Fotios and Yiorkas, Andrianos M and Karaman, Ibrahim and Elliott, Joshua and Luo, Qiang and Aeschbacher, Stefanie and Traci M Bartz and Baumeister, Sebastian E and Braund, Peter S and Brown, Michael R and Brody, Jennifer A and Clarke, Toni-Kim and Dimou, Niki and Jessica Faul and Homuth, Georg and Jackson, Anne U and Kentistou, Katherine A and Joshi, Peter K and Lemaitre, Rozenn N and Penelope A Lind and Lyytik{\"a}inen, Leo-Pekka and Mangino, Massimo and Milaneschi, Yuri and Nelson, Christopher P and Ilja M Nolte and Per{\"a}l{\"a}, Mia-Maria and Polasek, Ozren and David J Porteous and Scott M Ratliff and Smith, Jennifer A and Stan{\v c}{\'a}kov{\'a}, Alena and Teumer, Alexander and Tuominen, Samuli and Th{\'e}riault, S{\'e}bastien and Vangipurapu, Jagadish and Whitfield, John B and Wood, Alexis and Yao, Jie and Yu, Bing and Zhao, Wei and Dan E Arking and Auvinen, Juha and Liu, Chunyu and M{\"a}nnikk{\"o}, Minna and Risch, Lorenz and Rotter, Jerome I and Snieder, Harold and Veijola, Juha and Alexandra I Blakemore and Boehnke, Michael and Campbell, Harry and Conen, David and Johan G Eriksson and Hans-J{\"o}rgen Grabe and Guo, Xiuqing and van der Harst, Pim and Catharina A Hartman and Caroline Hayward and Andrew C Heath and J{\"a}rvelin, Marjo-Riitta and K{\"a}h{\"o}nen, Mika and Sharon L R Kardia and K{\"u}hne, Michael and Kuusisto, Johanna and Laakso, Markku and Lahti, Jari and Lehtim{\"a}ki, Terho and McIntosh, Andrew M and Mohlke, Karen L and Alanna C Morrison and Nicholas G Martin and Oldehinkel, Albertine J and Brenda W J H Penninx and Psaty, Bruce M and Olli T Raitakari and Rudan, Igor and Nilesh J Samani and Scott, Laura J and Timothy Spector and Verweij, Niek and David R Weir and James F Wilson and Levy, Daniel and Tzoulaki, Ioanna and Bell, Jimmy D and Matthews, Paul M and Rothenfluh, Adrian and Desrivi{\`e}res, Sylvane and Schumann, Gunter and Elliott, Paul} } @article {10712, title = {Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals.}, journal = {Nature Genetics}, volume = {50}, year = {2018}, month = {2018 07 23}, pages = {1112-1121}, abstract = {

Here we conducted a large-scale genetic association analysis of educational attainment in a sample of approximately 1.1 million individuals and identify 1,271 independent genome-wide-significant SNPs. For the SNPs taken together, we found evidence of heterogeneous effects across environments. The SNPs implicate genes involved in brain-development processes and neuron-to-neuron communication. In a separate analysis of the X chromosome, we identify 10 independent genome-wide-significant SNPs and estimate a SNP heritability of around 0.3\% in both men and women, consistent with partial dosage compensation. A joint (multi-phenotype) analysis of educational attainment and three related cognitive phenotypes generates polygenic scores that explain 11-13\% of the variance in educational attainment and 7-10\% of the variance in cognitive performance. This prediction accuracy substantially increases the utility of polygenic scores as tools in research.

}, keywords = {Adult, Aged, Aged, 80 and over, Cohort Studies, Educational Status, Female, Genome-Wide Association Study, Humans, Male, Middle Aged, Multifactorial Inheritance, Phenotype, Polymorphism, Single Nucleotide}, issn = {1546-1718}, doi = {10.1038/s41588-018-0147-3}, author = {Lee, James J and Wedow, Robbee and Okbay, Aysu and Kong, Edward and Maghzian, Omeed and Zacher, Meghan and Nguyen-Viet, Tuan Anh and Bowers, Peter and Sidorenko, Julia and Richard Karlsson Linn{\'e}r and Mark Alan Fontana and Kundu, Tushar and Lee, Chanwook and Hui Liu and Li, Ruoxi and Royer, Rebecca and Pascal N Timshel and Walters, Raymond K and Willoughby, Emily A and Yengo, Loic and Alver, Maris and Bao, Yanchun and Clark, David W and Day, Felix R and Furlotte, Nicholas A and Joshi, Peter K and Kathryn E Kemper and Kleinman, Aaron and Langenberg, Claudia and M{\"a}gi, Reedik and Joey W Trampush and Verma, Shefali Setia and Wu, Yang and Lam, Max and Jing Hua Zhao and Zheng, Zhili and Jason D Boardman and Campbell, Harry and Freese, Jeremy and Kathleen Mullan Harris and Caroline Hayward and Herd, Pamela and Kumari, Meena and Lencz, Todd and Luan, Jian{\textquoteright}an and Anil K. Malhotra and Andres Metspalu and Lili Milani and Ong, Ken K and Perry, John R B and David J Porteous and Ritchie, Marylyn D and Smart, Melissa C and Smith, Blair H and Tung, Joyce Y and Wareham, Nicholas J and James F Wilson and Jonathan P. Beauchamp and Dalton C Conley and T{\~o}nu Esko and Lehrer, Steven F and Patrik K E Magnusson and Oskarsson, Sven and Pers, Tune H and Matthew R Robinson and Thom, Kevin and Watson, Chelsea and Chabris, Christopher F and Meyer, Michelle N and David I Laibson and Yang, Jian and Johannesson, Magnus and Philipp D Koellinger and Turley, Patrick and Peter M Visscher and Daniel J. Benjamin and Cesarini, David} } @article {12139, title = {Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function.}, journal = {Nature Communications}, volume = {9}, year = {2018}, pages = {2098}, abstract = {

General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 {\texttimes} 10) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3\% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.

}, keywords = {Adolescent, Adult, Aged, Aged, 80 and over, Cognition, Genetic Loci, Genetic Predisposition to Disease, Humans, Mental Disorders, Middle Aged, Multifactorial Inheritance, Neurodegenerative Diseases, Neurodevelopmental Disorders, Polymorphism, Single Nucleotide, Reaction Time, Young Adult}, issn = {2041-1723}, doi = {10.1038/s41467-018-04362-x}, author = {Gail Davies and Lam, Max and Sarah E Harris and Joey W Trampush and Luciano, Michelle and W David Hill and Hagenaars, Saskia P and Ritchie, Stuart J and Riccardo E Marioni and Fawns-Ritchie, Chloe and David C Liewald and Okely, Judith A and Ahola-Olli, Ari V and Barnes, Catriona L K and Bertram, Lars and Joshua C. Bis and Katherine E Burdick and Christoforou, Andrea and DeRosse, Pamela and Djurovic, Srdjan and Espeseth, Thomas and Giakoumaki, Stella and Giddaluru, Sudheer and Gustavson, Daniel E and Caroline Hayward and Edith Hofer and Ikram, M Arfan and Karlsson, Robert and Knowles, Emma and Lahti, Jari and Leber, Markus and Li, Shuo and Mather, Karen A and Melle, Ingrid and Morris, Derek and Christopher J Oldmeadow and Palviainen, Teemu and Payton, Antony and Pazoki, Raha and Katja E Petrovic and Chandra A Reynolds and Sargurupremraj, Muralidharan and Scholz, Markus and Smith, Jennifer A and Smith, Albert V and Terzikhan, Natalie and Thalamuthu, Anbupalam and Trompet, Stella and Sven J van der Lee and Erin B Ware and Windham, B Gwen and Margaret J Wright and Yang, Jingyun and Yu, Jin and Ames, David and Amin, Najaf and Amouyel, Philippe and Andreassen, Ole A and Armstrong, Nicola J and Assareh, Amelia A and John R. Attia and Attix, Deborah and Avramopoulos, Dimitrios and David A Bennett and B{\"o}hmer, Anne C and Patricia A. Boyle and Brodaty, Henry and Campbell, Harry and Tyrone D. Cannon and Elizabeth T. Cirulli and Congdon, Eliza and Conley, Emily Drabant and Corley, Janie and Cox, Simon R and Dale, Anders M and Dehghan, Abbas and Danielle M. Dick and Dickinson, Dwight and Johan G Eriksson and Evangelou, Evangelos and Jessica Faul and Ford, Ian and Nelson A. Freimer and Gao, He and Giegling, Ina and Gillespie, Nathan A and Gordon, Scott D and Gottesman, Rebecca F and Michael E Griswold and Gudnason, Vilmundur and Tamara B Harris and Hartmann, Annette M and Hatzimanolis, Alex and Gerardo Heiss and Holliday, Elizabeth G and Joshi, Peter K and K{\"a}h{\"o}nen, Mika and Sharon L R Kardia and Ida Karlsson and Kleineidam, Luca and David S Knopman and Kochan, Nicole A and Konte, Bettina and Kwok, John B and Stephanie Le Hellard and Lee, Teresa and Lehtim{\"a}ki, Terho and Li, Shu-Chen and Lill, Christina M and Liu, Tian and Koini, Marisa and London, Edythe and Longstreth, Will T and Lopez, Oscar L and Loukola, Anu and Luck, Tobias and Astri J Lundervold and Lundquist, Anders and Lyytik{\"a}inen, Leo-Pekka and Nicholas G Martin and Grant W Montgomery and Murray, Alison D and Anna C Need and Noordam, Raymond and Nyberg, Lars and William E R Ollier and Papenberg, Goran and Pattie, Alison and Polasek, Ozren and Russell A Poldrack and Psaty, Bruce M and Reppermund, Simone and Steffi G Riedel-Heller and Rose, Richard J and Rotter, Jerome I and Roussos, Panos and Rovio, Suvi P and Saba, Yasaman and Fred W Sabb and Sachdev, Perminder S and Satizabal, Claudia L and Schmid, Matthias and Rodney J Scott and Matthew A Scult and Simino, Jeannette and Slagboom, P Eline and Smyrnis, Nikolaos and Soumar{\'e}, A{\"\i}cha and Nikos C Stefanis and Stott, David J and Richard E Straub and Sundet, Kjetil and Taylor, Adele M and Kent D Taylor and Tzoulaki, Ioanna and Tzourio, Christophe and Andr{\'e} G Uitterlinden and Vitart, Veronique and Aristotle N Voineskos and Kaprio, Jaakko and Wagner, Michael and Wagner, Holger and Weinhold, Leonie and Wen, K Hoyan and Elisabeth Widen and Yang, Qiong and Zhao, Wei and Hieab H Adams and Dan E Arking and Robert M Bilder and Bitsios, Panos and Boerwinkle, Eric and Chiba-Falek, Ornit and Corvin, Aiden and Philip L de Jager and Debette, St{\'e}phanie and Donohoe, Gary and Elliott, Paul and Fitzpatrick, Annette L and Gill, Michael and David C. Glahn and H{\"a}gg, Sara and Narelle K Hansell and Ahmad R Hariri and Ikram, M Kamran and Jukema, J Wouter and Vuoksimaa, Eero and Matthew C Keller and Kremen, William S and Lenore J Launer and Lindenberger, Ulman and Aarno Palotie and Nancy L Pedersen and Pendleton, Neil and David J Porteous and Katri R{\"a}ikk{\"o}nen and Olli T Raitakari and Ramirez, Alfredo and Reinvang, Ivar and Rudan, Igor and Schmidt, Reinhold and Schmidt, Helena and Peter W Schofield and Peter R Schofield and John M Starr and Vidar M Steen and Trollor, Julian N and Turner, Steven T and Cornelia M van Duijn and Villringer, Arno and Daniel R Weinberger and David R Weir and James F Wilson and Anil K. Malhotra and McIntosh, Andrew M and Gale, Catharine R and Seshadri, Sudha and Thomas H Mosley and Bressler, Jan and Lencz, Todd and Ian J Deary} } @article {12131, title = {Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity.}, journal = {Nature Communications}, volume = {8}, year = {2017}, pages = {910}, abstract = {

Genomic analysis of longevity offers the potential to illuminate the biology of human aging. Here, using genome-wide association meta-analysis of 606,059 parents{\textquoteright} survival, we discover two regions associated with longevity (HLA-DQA1/DRB1 and LPA). We also validate previous suggestions that APOE, CHRNA3/5, CDKN2A/B, SH2B3 and FOXO3A influence longevity. Next we show that giving up smoking, educational attainment, openness to new experience and high-density lipoprotein (HDL) cholesterol levels are most positively genetically correlated with lifespan while susceptibility to coronary artery disease (CAD), cigarettes smoked per day, lung cancer, insulin resistance and body fat are most negatively correlated. We suggest that the effect of education on lifespan is principally mediated through smoking while the effect of obesity appears to act via CAD. Using instrumental variables, we suggest that an increase of one body mass index unit reduces lifespan by 7 months while 1 year of education adds 11 months to expected lifespan.Variability in human longevity is genetically influenced. Using genetic data of parental lifespan, the authors identify associations at HLA-DQA/DRB1 and LPA and find that genetic variants that increase educational attainment have a positive effect on lifespan whereas increasing BMI negatively affects lifespan.

}, keywords = {Alleles, Body Mass Index, Coronary Disease, Education, Genetic Predisposition to Disease, Genome-Wide Association Study, HLA-DQ alpha-Chains, HLA-DRB1 Chains, Humans, Insulin Resistance, Life Style, Lipoprotein(a), Lipoproteins, HDL, Longevity, Lung Neoplasms, Obesity, Polymorphism, Single Nucleotide, Smoking, Socioeconomic factors}, issn = {2041-1723}, doi = {10.1038/s41467-017-00934-5}, author = {Joshi, Peter K and Nicola Pirastu and Kentistou, Katherine A and Fischer, Krista and Edith Hofer and Schraut, Katharina E and Clark, David W and Nutile, Teresa and Barnes, Catriona L K and Paul Rhj Timmers and Shen, Xia and Gandin, Ilaria and McDaid, Aaron F and Hansen, Thomas Folkmann and Gordon, Scott D and Giulianini, Franco and Boutin, Thibaud S and Abdellaoui, Abdel and Zhao, Wei and Medina-Gomez, Carolina and Traci M Bartz and Trompet, Stella and Leslie A Lange and Raffield, Laura and van der Spek, Ashley and Galesloot, Tessel E and Proitsi, Petroula and Yanek, Lisa R and Bielak, Lawrence F and Payton, Antony and Murgia, Federico and Concas, Maria Pina and Biino, Ginevra and Tajuddin, Salman M and Sepp{\"a}l{\"a}, Ilkka and Amin, Najaf and Boerwinkle, Eric and B{\o}rglum, Anders D and Campbell, Archie and Ellen W Demerath and Demuth, Ilja and Jessica Faul and Ford, Ian and Gialluisi, Alessandro and G{\"o}gele, Martin and Graff, Mariaelisa and Aroon Hingorani and Jouke-Jan Hottenga and Hougaard, David M and Hurme, Mikko A and Ikram, M Arfan and Jylh{\"a}, Marja and Kuh, Diana and Ligthart, Lannie and Lill, Christina M and Lindenberger, Ulman and Lumley, Thomas and M{\"a}gi, Reedik and Marques-Vidal, Pedro and Sarah E Medland and Lili Milani and Nagy, Reka and William E R Ollier and Peyser, Patricia A and Pramstaller, Peter P and Ridker, Paul M and Fernando Rivadeneira and Ruggiero, Daniela and Saba, Yasaman and Schmidt, Reinhold and Schmidt, Helena and Slagboom, P Eline and Smith, Blair H and Smith, Jennifer A and Sotoodehnia, Nona and Steinhagen-Thiessen, Elisabeth and van Rooij, Frank J A and Verbeek, Andr{\'e} L and Vermeulen, Sita H and Vollenweider, Peter and Wang, Yunpeng and Werge, Thomas and Whitfield, John B and Alan B Zonderman and Lehtim{\"a}ki, Terho and Michele K Evans and Pirastu, Mario and Fuchsberger, Christian and Bertram, Lars and Pendleton, Neil and Sharon L R Kardia and Ciullo, Marina and Becker, Diane M and Wong, Andrew and Psaty, Bruce M and Cornelia M van Duijn and Wilson, James G and Jukema, J Wouter and Lambertus A Kiemeney and Andr{\'e} G Uitterlinden and Franceschini, Nora and Kari E North and David R Weir and Andres Metspalu and Dorret I Boomsma and Caroline Hayward and Daniel I Chasman and Nicholas G Martin and Sattar, Naveed and Campbell, Harry and T{\~o}nu Esko and Kutalik, Zolt{\'a}n and James F Wilson} } @article {8881, title = {Genome-wide analysis identifies 12 loci influencing human reproductive behavior.}, journal = {Nat Genet}, volume = {48}, year = {2016}, month = {2016 Dec}, pages = {1462-1472}, abstract = {

The genetic architecture of human reproductive behavior-age at first birth (AFB) and number of children ever born (NEB)-has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the underlying mechanisms of AFB and NEB are poorly understood. We report a large genome-wide association study of both sexes including 251,151 individuals for AFB and 343,072 individuals for NEB. We identified 12 independent loci that are significantly associated with AFB and/or NEB in a SNP-based genome-wide association study and 4 additional loci associated in a gene-based effort. These loci harbor genes that are likely to have a role, either directly or by affecting non-local gene expression, in human reproduction and infertility, thereby increasing understanding of these complex traits.

}, issn = {1546-1718}, doi = {10.1038/ng.3698}, author = {Nicola Barban and Jansen, Rick and de Vlaming, Ronald and Vaez, Ahmad and Mandemakers, Jornt J and Felix C Tropf and Shen, Xia and James F Wilson and Daniel I Chasman and Ilja M Nolte and Tragante, Vinicius and van der Laan, Sander W and Perry, John R B and Kong, Augustine and Ahluwalia, Tarunveer S and Albrecht, Eva and Laura M Yerges-Armstrong and Atzmon, Gil and Auro, Kirsi and Kristin L. Ayers and Bakshi, Andrew and Ben-Avraham, Danny and Klaus Berger and Bergman, Aviv and Bertram, Lars and Bielak, Lawrence F and Bjornsdottir, Gyda and Bonder, Marc Jan and Broer, Linda and Bui, Minh and Barbieri, Caterina and Cavadino, Alana and Chavarro, Jorge E and Turman, Constance and Maria Pina Concas and Cordell, Heather J and Gail Davies and Eibich, Peter and Eriksson, Nicholas and T{\~o}nu Esko and Eriksson, Joel and Falahi, Fahimeh and Felix, Janine F and Mark Alan Fontana and Lude L Franke and Gandin, Ilaria and Gaskins, Audrey J and Gieger, Christian and Gunderson, Erica P and Guo, Xiuqing and Caroline Hayward and He, Chunyan and Edith Hofer and Huang, Hongyan and Joshi, Peter K and Kanoni, Stavroula and Karlsson, Robert and Kiechl, Stefan and Kifley, Annette and Kluttig, Alexander and Kraft, Peter and Lagou, Vasiliki and Lecoeur, Cecile and Lahti, Jari and Li-Gao, Ruifang and Penelope A Lind and Tian Liu and Makalic, Enes and Mamasoula, Crysovalanto and Lindsay K Matteson and Mbarek, Hamdi and McArdle, Patrick F and McMahon, George and Meddens, S Fleur W and Mihailov, Evelin and Michael B Miller and Missmer, Stacey A and Monnereau, Claire and van der Most, Peter J and Myhre, Ronny and Michael A Nalls and Nutile, Teresa and Ioanna Panagiota Kalafati and Porcu, Eleonora and Prokopenko, Inga and Rajan, Kumar B and Rich-Edwards, Janet and Cornelius A Rietveld and Robino, Antonietta and Rose, Lynda M and Rueedi, Rico and Ryan, Kathleen A and Saba, Yasaman and Schmidt, Daniel and Jennifer A Smith and Stolk, Lisette and Streeten, Elizabeth and T{\"o}njes, Anke and Thorleifsson, Gudmar and Ulivi, Sheila and Wedenoja, Juho and J{\"u}rgen Wellmann and Willeit, Peter and Yao, Jie and Yengo, Loic and Jing Hua Zhao and Wei Zhao and Zhernakova, Daria V and Amin, Najaf and Andrews, Howard and Balkau, Beverley and Barzilai, Nir and Bergmann, Sven and Biino, Ginevra and Bisgaard, Hans and B{\o}nnelykke, Klaus and Dorret I Boomsma and Buring, Julie E and Campbell, Harry and Cappellani, Stefania and Ciullo, Marina and Cox, Simon R and Francesco Cucca and Toniolo, Daniela and Davey-Smith, George and Ian J Deary and George Dedoussis and Deloukas, Panos and Cornelia M van Duijn and Eco J. C. de Geus and Johan G Eriksson and Jessica Faul and Cinzia Felicita Sala and Froguel, Philippe and Paolo P. Gasparini and Giorgia G Girotto and Hans-J{\"o}rgen Grabe and Greiser, Karin Halina and Groenen, Patrick J F and de Haan, Hugoline G and Haerting, Johannes and Tamara B Harris and Andrew C Heath and Heikkil{\"a}, Kauko and Hofman, Albert and Homuth, Georg and Holliday, Elizabeth G and John L Hopper and Hypp{\"o}nen, Elina and Jacobsson, Bo and Vincent Jaddoe and Johannesson, Magnus and Jugessur, Astanand and K{\"a}h{\"o}nen, Mika and Kajantie, Eero and Sharon L R Kardia and Keavney, Bernard and Kolcic, Ivana and Koponen, P{\"a}ivikki and Kovacs, Peter and Kronenberg, Florian and Kutalik, Zolt{\'a}n and La Bianca, Martina and Lachance, Genevieve and Iacono, William G and Lai, Sandra and Lehtim{\"a}ki, Terho and David C Liewald and Lindgren, Cecilia M and Yongmei Liu and Luben, Robert and Lucht, Michael and Luoto, Riitta and Magnus, Per and Patrik K E Magnusson and Nicholas G Martin and McGue, Matt and McQuillan, Ruth and Sarah E Medland and Meisinger, Christa and Mellstr{\"o}m, Dan and Andres Metspalu and Traglia, Michela and Lili Milani and Mitchell, Paul and Grant W Montgomery and Dennis O Mook-Kanamori and de Mutsert, Ren{\'e}e and Nohr, Ellen A and Ohlsson, Claes and Olsen, J{\o}rn and Ong, Ken K and Paternoster, Lavinia and Pattie, Alison and Brenda W J H Penninx and Markus Perola and Peyser, Patricia A and Pirastu, Mario and Polasek, Ozren and Power, Chris and Kaprio, Jaakko and Raffel, Leslie J and Katri R{\"a}ikk{\"o}nen and Olli T Raitakari and Ridker, Paul M and Ring, Susan M and Roll, Kathryn and Rudan, Igor and Ruggiero, Daniela and Rujescu, Dan and Veikko Salomaa and Schlessinger, David and Schmidt, Helena and Schmidt, Reinhold and Schupf, Nicole and Johannes H Smit and Sorice, Rossella and Timothy Spector and John M Starr and St{\"o}ckl, Doris and Strauch, Konstantin and Stumvoll, Michael and Swertz, Morris A and Thorsteinsdottir, Unnur and A. Roy Thurik and Nicholas J Timpson and Tung, Joyce Y and Andr{\'e} G Uitterlinden and Vaccargiu, Simona and Viikari, Jorma and Vitart, Veronique and V{\"o}lzke, Henry and Vollenweider, Peter and Vuckovic, Dragana and Waage, Johannes and Wagner, Gert G and Wang, Jie Jin and Wareham, Nicholas J and David R Weir and Gonneke Willemsen and Willeit, Johann and Alan F Wright and Krina T Zondervan and Stefansson, Kari and Krueger, Robert F and Lee, James J and Daniel J. Benjamin and Cesarini, David and Philipp D Koellinger and den Hoed, Marcel and Snieder, Harold and Melinda C Mills} } @article {8883, title = {Genome-wide association study identifies 74 loci associated with educational attainment.}, journal = {Nature}, volume = {533}, year = {2016}, month = {2016 05 26}, pages = {539-42}, abstract = {

Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20\% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.

}, keywords = {Alzheimer{\textquoteright}s disease, Bipolar Disorder, Cognitive Ability, Education, Fetus, Genome-Wide Association Study, Humans, Molecular Sequence Annotation, Polymorphism, Single Nucleotide, Schizophrenia, United Kingdom}, issn = {1476-4687}, doi = {10.1038/nature17671}, author = {Okbay, Aysu and Jonathan P. Beauchamp and Mark Alan Fontana and Lee, James J and Pers, Tune H and Cornelius A Rietveld and Turley, Patrick and Chen, Guo-Bo and Emilsson, Valur and Meddens, S Fleur W and Oskarsson, Sven and Pickrell, Joseph K and Thom, Kevin and Pascal N Timshel and de Vlaming, Ronald and Abdel Abdellaoui and Ahluwalia, Tarunveer S and Bacelis, Jonas and Baumbach, Clemens and Bjornsdottir, Gyda and Brandsma, Johannes H and Maria Pina Concas and Derringer, Jaime and Furlotte, Nicholas A and Galesloot, Tessel E and Giorgia G Girotto and Gupta, Richa and Hall, Leanne M and Sarah E Harris and Edith Hofer and Horikoshi, Momoko and Huffman, Jennifer E and Kaasik, Kadri and Ioanna Panagiota Kalafati and Karlsson, Robert and Kong, Augustine and Lahti, Jari and Sven J van der Lee and Christiaan de Leeuw and Penelope A Lind and Lindgren, Karl-Oskar and Tian Liu and Mangino, Massimo and Marten, Jonathan and Mihailov, Evelin and Michael B Miller and van der Most, Peter J and Christopher J Oldmeadow and Payton, Antony and Pervjakova, Natalia and Wouter J Peyrot and Qian, Yong and Olli T Raitakari and Rueedi, Rico and Salvi, Erika and Schmidt, B{\"o}rge and Schraut, Katharina E and Jianxin Shi and Albert Vernon Smith and Poot, Raymond A and St Pourcain, Beate and Teumer, Alexander and Thorleifsson, Gudmar and Verweij, Niek and Vuckovic, Dragana and J{\"u}rgen Wellmann and Westra, Harm-Jan and Yang, Jingyun and Wei Zhao and Zhihong Zhu and Alizadeh, Behrooz Z and Amin, Najaf and Bakshi, Andrew and Baumeister, Sebastian E and Biino, Ginevra and B{\o}nnelykke, Klaus and Patricia A. Boyle and Campbell, Harry and Cappuccio, Francesco P and Gail Davies and De Neve, Jan-Emmanuel and Deloukas, Panos and Demuth, Ilja and Ding, Jun and Eibich, Peter and Eisele, Lewin and Eklund, Niina and Jessica Faul and Feitosa, Mary F and Andreas J Forstner and Gandin, Ilaria and Gunnarsson, Bjarni and Halld{\'o}rsson, Bjarni V and Tamara B Harris and Andrew C Heath and Lynne J Hocking and Holliday, Elizabeth G and Homuth, Georg and Horan, Michael A and Jouke-Jan Hottenga and Philip L de Jager and Joshi, Peter K and Jugessur, Astanand and Marika A Kaakinen and K{\"a}h{\"o}nen, Mika and Kanoni, Stavroula and Keltigangas-J{\"a}rvinen, Liisa and Lambertus A Kiemeney and Kolcic, Ivana and Koskinen, Seppo and Kraja, Aldi T and Kroh, Martin and Kutalik, Zolt{\'a}n and Latvala, Antti and Lenore J Launer and Lebreton, Ma{\"e}l P and Douglas F Levinson and Paul Lichtenstein and Lichtner, Peter and David C Liewald and Loukola, Anu and Pamela A F Madden and M{\"a}gi, Reedik and M{\"a}ki-Opas, Tomi and Riccardo E Marioni and Marques-Vidal, Pedro and Meddens, Gerardus A and McMahon, George and Meisinger, Christa and Meitinger, Thomas and Milaneschi, Yusplitri and Lili Milani and Grant W Montgomery and Myhre, Ronny and Nelson, Christopher P and Nyholt, Dale R and William E R Ollier and Aarno Palotie and Paternoster, Lavinia and Nancy L Pedersen and Katja E Petrovic and David J Porteous and Katri R{\"a}ikk{\"o}nen and Ring, Susan M and Robino, Antonietta and Rostapshova, Olga and Rudan, Igor and Rustichini, Aldo and Veikko Salomaa and Sanders, Alan R and Sarin, Antti-Pekka and Schmidt, Helena and Rodney J Scott and Smith, Blair H and Jennifer A Smith and Staessen, Jan A and Steinhagen-Thiessen, Elisabeth and Strauch, Konstantin and Antonio Terracciano and Tobin, Martin D and Ulivi, Sheila and Vaccargiu, Simona and Quaye, Lydia and van Rooij, Frank J A and Venturini, Cristina and Anna A E Vinkhuyzen and V{\"o}lker, Uwe and V{\"o}lzke, Henry and Vonk, Judith M and Vozzi, Diego and Waage, Johannes and Erin B Ware and Gonneke Willemsen and John R. Attia and David A Bennett and Klaus Berger and Bertram, Lars and Bisgaard, Hans and Dorret I Boomsma and Ingrid B Borecki and B{\"u}ltmann, Ute and Chabris, Christopher F and Francesco Cucca and Cusi, Daniele and Ian J Deary and George Dedoussis and Cornelia M van Duijn and Johan G Eriksson and Franke, Barbara and Lude L Franke and Paolo P. Gasparini and Gejman, Pablo V and Gieger, Christian and Hans-J{\"o}rgen Grabe and Gratten, Jacob and Groenen, Patrick J F and Gudnason, Vilmundur and van der Harst, Pim and Caroline Hayward and Hinds, David A and Hoffmann, Wolfgang and Hypp{\"o}nen, Elina and Iacono, William G and Jacobsson, Bo and J{\"a}rvelin, Marjo-Riitta and J{\"o}ckel, Karl-Heinz and Kaprio, Jaakko and Sharon L R Kardia and Lehtim{\"a}ki, Terho and Lehrer, Steven F and Patrik K E Magnusson and Nicholas G Martin and McGue, Matt and Andres Metspalu and Pendleton, Neil and Brenda W J H Penninx and Markus Perola and Nicola Pirastu and Pirastu, Mario and Polasek, Ozren and Posthuma, Danielle and Power, Christine and Province, Michael A and Nilesh J Samani and Schlessinger, David and Schmidt, Reinhold and Thorkild I. A. S{\o}rensen and Timothy Spector and Stefansson, Kari and Thorsteinsdottir, Unnur and A. Roy Thurik and Nicholas J Timpson and Henning Tiemeier and Tung, Joyce Y and Andr{\'e} G Uitterlinden and Vitart, Veronique and Vollenweider, Peter and David R Weir and James F Wilson and Alan F Wright and Dalton C Conley and Krueger, Robert F and George Davey Smith and Hofman, Albert and David I Laibson and Sarah E Medland and Meyer, Michelle N and Yang, Jian and Johannesson, Magnus and Peter M Visscher and T{\~o}nu Esko and Philipp D Koellinger and Cesarini, David and Daniel J. Benjamin} } @article {8884, title = {Directional dominance on stature and cognition in~diverse human populations.}, journal = {Nature}, volume = {523}, year = {2015}, month = {2015 Jul 23}, pages = {459-62}, abstract = {

Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs~of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 {\texttimes} 10(-300), 2.1 {\texttimes} 10(-6), 2.5 {\texttimes} 10(-10) and 1.8 {\texttimes} 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months{\textquoteright} less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.

}, keywords = {Biological Evolution, Blood pressure, Body Height, Cholesterol, Cognitive Ability, Cohort Studies, Education, Female, Forced Expiratory Volume, Genome, Homozygote, Humans, Lung Volume Measurements, Male, Phenotype}, issn = {1476-4687}, doi = {10.1038/nature14618}, author = {Joshi, Peter K and T{\~o}nu Esko and Mattsson, Hannele and Eklund, Niina and Gandin, Ilaria and Nutile, Teresa and Jackson, Anne U and Schurmann, Claudia and Albert Vernon Smith and Zhang, Weihua and Okada, Yukinori and Stan{\v c}{\'a}kov{\'a}, Alena and Jessica Faul and Wei Zhao and Traci M Bartz and Maria Pina Concas and Franceschini, Nora and Enroth, Stefan and Vitart, Veronique and Trompet, Stella and Guo, Xiuqing and Daniel I Chasman and Jeff O{\textquoteright}Connell and Corre, Tanguy and Nongmaithem, Suraj S and Chen, Yuning and Mangino, Massimo and Ruggiero, Daniela and Traglia, Michela and Farmaki, Aliki-Eleni and Kacprowski, Tim and Bjonnes, Andrew and van der Spek, Ashley and Wu, Ying and Giri, Anil K and Yanek, Lisa R and Wang, Lihua and Edith Hofer and Cornelius A Rietveld and McLeod, Olga and Marilyn C Cornelis and Pattaro, Cristian and Verweij, Niek and Baumbach, Clemens and Abdel Abdellaoui and Warren, Helen R and Vuckovic, Dragana and Mei, Hao and Bouchard, Claude and Perry, John R B and Cappellani, Stefania and Saira S Mirza and Benton, Miles C and Broeckel, Ulrich and Sarah E Medland and Penelope A Lind and Malerba, Giovanni and Alexander W Drong and Yengo, Loic and Bielak, Lawrence F and Zhi, Degui and van der Most, Peter J and Daniel Shriner and M{\"a}gi, Reedik and Hemani, Gibran and Karaderi, Tugce and Wang, Zhaoming and Tian Liu and Demuth, Ilja and Jing Hua Zhao and Meng, Weihua and Lataniotis, Lazaros and van der Laan, Sander W and Bradfield, Jonathan P and Andrew R Wood and Bonnefond, Amelie and Ahluwalia, Tarunveer S and Hall, Leanne M and Salvi, Erika and Yazar, Seyhan and Carstensen, Lisbeth and de Haan, Hugoline G and Abney, Mark and Afzal, Uzma and Matthew A. Allison and Amin, Najaf and Asselbergs, Folkert W and Bakker, Stephan J L and Barr, R Graham and Baumeister, Sebastian E and Daniel J. Benjamin and Bergmann, Sven and Boerwinkle, Eric and Erwin P Bottinger and Campbell, Archie and Chakravarti, Aravinda and Chan, Yingleong and Chanock, Stephen J and Chen, Constance and Yii-Der I Chen and Collins, Francis S and Connell, John and Correa, Adolfo and Cupples, L Adrienne and Gail Davies and D{\"o}rr, Marcus and Georg B Ehret and Ellis, Stephen B and Feenstra, Bjarke and Feitosa, Mary F and Ford, Ian and Caroline S Fox and Timothy M Frayling and Friedrich, Nele and Geller, Frank and Scotland, Generation and Gillham-Nasenya, Irina and Gottesman, Omri and Graff, Misa and Grodstein, Francine and Gu, Charles and Haley, Chris and Hammond, Christopher J and Sarah E Harris and Tamara B Harris and Nicholas D Hastie and Heard-Costa, Nancy L and Heikkil{\"a}, Kauko and Lynne J Hocking and Homuth, Georg and Jouke-Jan Hottenga and Huang, Jinyan and Huffman, Jennifer E and Hysi, Pirro G and Mohammed Arfan Ikram and Ingelsson, Erik and Joensuu, Anni and Johansson, {\r A}sa and Jousilahti, Pekka and Jukema, J Wouter and K{\"a}h{\"o}nen, Mika and Kamatani, Yoichiro and Kanoni, Stavroula and Kerr, Shona M and Khan, Nazir M and Philipp D Koellinger and Koistinen, Heikki A and Kooner, Manraj K and Kubo, Michiaki and Kuusisto, Johanna and Lahti, Jari and Lenore J Launer and Lea, Rodney A and Lehne, Benjamin and Lehtim{\"a}ki, Terho and David C Liewald and Lars Lind and Loh, Marie and Lokki, Marja-Liisa and London, Stephanie J and Loomis, Stephanie J and Loukola, Anu and Lu, Yingchang and Lumley, Thomas and Lundqvist, Annamari and M{\"a}nnist{\"o}, Satu and Marques-Vidal, Pedro and Masciullo, Corrado and Matchan, Angela and Mathias, Rasika A and Matsuda, Koichi and Meigs, James B and Meisinger, Christa and Meitinger, Thomas and Menni, Cristina and Mentch, Frank D and Mihailov, Evelin and Lili Milani and Montasser, May E and Grant W Montgomery and Alanna C Morrison and Myers, Richard H and Nadukuru, Rajiv and Navarro, Pau and Nelis, Mari and Nieminen, Markku S and Ilja M Nolte and O{\textquoteright}Connor, George T and Ogunniyi, Adesola and Padmanabhan, Sandosh and Walter R Palmas and Pankow, James S and Patarcic, Inga and Pavani, Francesca and Peyser, Patricia A and Pietilainen, Kirsi and Neil Poulter and Prokopenko, Inga and Ralhan, Sarju and Redmond, Paul and Rich, Stephen S and Rissanen, Harri and Robino, Antonietta and Rose, Lynda M and Rose, Richard and Cinzia Felicita Sala and Babatunde Salako and Veikko Salomaa and Sarin, Antti-Pekka and Saxena, Richa and Schmidt, Helena and Scott, Laura J and Scott, William R and Sennblad, Bengt and Seshadri, Sudha and Peter Sever and Shrestha, Smeeta and Smith, Blair H and Jennifer A Smith and Soranzo, Nicole and Sotoodehnia, Nona and Southam, Lorraine and Stanton, Alice V and Stathopoulou, Maria G and Strauch, Konstantin and Strawbridge, Rona J and Suderman, Matthew J and Tandon, Nikhil and Tang, Sian-Tsun and Kent D Taylor and Bamidele O Tayo and T{\"o}glhofer, Anna Maria and Tomaszewski, Maciej and T{\v s}ernikova, Natalia and Tuomilehto, Jaakko and Andr{\'e} G Uitterlinden and Vaidya, Dhananjay and van Hylckama Vlieg, Astrid and van Setten, Jessica and Vasankari, Tuula and Vedantam, Sailaja and Vlachopoulou, Efthymia and Vozzi, Diego and Vuoksimaa, Eero and Waldenberger, Melanie and Erin B Ware and Wentworth-Shields, William and Whitfield, John B and Sarah Wild and Gonneke Willemsen and Yajnik, Chittaranjan S and Yao, Jie and Zaza, Gianluigi and Zhu, Xiaofeng and Salem, Rany M and Melbye, Mads and Bisgaard, Hans and Nilesh J Samani and Cusi, Daniele and Mackey, David A and Cooper, Richard S and Froguel, Philippe and Pasterkamp, Gerard and Grant, Struan F A and Hakonarson, Hakon and Luigi Ferrucci and Scott, Robert A and Morris, Andrew D and Palmer, Colin N A and George Dedoussis and Deloukas, Panos and Bertram, Lars and Lindenberger, Ulman and Berndt, Sonja I and Lindgren, Cecilia M and Nicholas J Timpson and T{\"o}njes, Anke and Munroe, Patricia B and Thorkild I. A. S{\o}rensen and Charles N Rotimi and Donna K Arnett and Oldehinkel, Albertine J and Sharon L R Kardia and Balkau, Beverley and Gambaro, Giovanni and Morris, Andrew P and Johan G Eriksson and Margaret J Wright and Nicholas G Martin and Hunt, Steven C and John M Starr and Ian J Deary and Griffiths, Lyn R and Henning Tiemeier and Nicola Pirastu and Kaprio, Jaakko and Wareham, Nicholas J and P{\'e}russe, Louis and Wilson, James G and Giorgia G Girotto and Caulfield, Mark J and Olli T Raitakari and Dorret I Boomsma and Gieger, Christian and van der Harst, Pim and Hicks, Andrew A and Kraft, Peter and Sinisalo, Juha and Knekt, Paul and Johannesson, Magnus and Patrik K E Magnusson and Hamsten, Anders and Schmidt, Reinhold and Ingrid B Borecki and Vartiainen, Erkki and Becker, Diane M and Bharadwaj, Dwaipayan and Mohlke, Karen L and Boehnke, Michael and Cornelia M van Duijn and Sanghera, Dharambir K and Teumer, Alexander and Zeggini, Eleftheria and Andres Metspalu and Paolo P. Gasparini and Ulivi, Sheila and Ober, Carole and Toniolo, Daniela and Rudan, Igor and David J Porteous and Ciullo, Marina and Timothy Spector and Caroline Hayward and Dupuis, Jos{\'e}e and Ruth J F Loos and Alan F Wright and Chandak, Giriraj R and Vollenweider, Peter and Alan R Shuldiner and Ridker, Paul M and Rotter, Jerome I and Sattar, Naveed and Gyllensten, Ulf and Kari E North and Pirastu, Mario and Psaty, Bruce M and David R Weir and Laakso, Markku and Gudnason, Vilmundur and Takahashi, Atsushi and Chambers, John C and Kooner, Jaspal S and David P Strachan and Campbell, Harry and Joel N Hirschhron and Markus Perola and Polasek, Ozren and James F Wilson} } @article {8620, title = {GWAS of 126,559 individuals identifies genetic variants associated with educational attainment.}, journal = {Science}, volume = {340}, year = {2013}, month = {2013 Jun 21}, pages = {1467-71}, abstract = {

A genome-wide association study (GWAS) of educational attainment was conducted in a discovery sample of 101,069 individuals and a replication sample of 25,490. Three independent single-nucleotide polymorphisms (SNPs) are genome-wide significant (rs9320913, rs11584700, rs4851266), and all three replicate. Estimated effects sizes are small (coefficient of determination R(2) ≈ 0.02\%), approximately 1 month of schooling per allele. A linear polygenic score from all measured SNPs accounts for ≈2\% of the variance in both educational attainment and cognitive function. Genes in the region of the loci have previously been associated with health, cognitive, and central nervous system phenotypes, and bioinformatics analyses suggest the involvement of the anterior caudate nucleus. These findings provide promising candidate SNPs for follow-up work, and our effect size estimates can anchor power analyses in social-science genetics.

}, keywords = {Cognition, Educational Status, Endophenotypes, Female, Genetic Loci, Genome-Wide Association Study, Humans, Male, Multifactorial Inheritance, Polymorphism, Single Nucleotide}, issn = {1095-9203}, doi = {10.1126/science.1235488}, author = {Cornelius A Rietveld and Sarah E Medland and Derringer, Jaime and Yang, Jian and T{\~o}nu Esko and Martin, Nicolas W and Westra, Harm-Jan and Shakhbazov, Konstantin and Abdel Abdellaoui and Agrawal, Arpana and Albrecht, Eva and Alizadeh, Behrooz Z and Amin, Najaf and Barnard, John and Baumeister, Sebastian E and Benke, Kelly S and Bielak, Lawrence F and Boatman, Jeffrey A and Patricia A. Boyle and Gail Davies and Christiaan de Leeuw and Eklund, Niina and Daniel S Evans and Rudolf Ferhmann and Fischer, Krista and Gieger, Christian and Gjessing, H{\r a}kon K and H{\"a}gg, Sara and Harris, Jennifer R and Caroline Hayward and Holzapfel, Christina and Carla A Ibrahim-Verbaas and Ingelsson, Erik and Jacobsson, Bo and Joshi, Peter K and Jugessur, Astanand and Marika A Kaakinen and Kanoni, Stavroula and Karjalainen, Juha and Kolcic, Ivana and Kristiansson, Kati and Kutalik, Zolt{\'a}n and J. Lahti and Lee, Sang H and Lin, Peng and Penelope A Lind and Yongmei Liu and Kurt Lohman and Loitfelder, Marisa and McMahon, George and Vidal, Pedro Marques and Osorio Meirelles and Lili Milani and Myhre, Ronny and Nuotio, Marja-Liisa and Christopher J Oldmeadow and Katja E Petrovic and Wouter J Peyrot and Polasek, Ozren and Quaye, Lydia and Reinmaa, Eva and Rice, John P and Rizzi, Thais S and Schmidt, Helena and Schmidt, Reinhold and Albert Vernon Smith and Jennifer A Smith and Toshiko Tanaka and Antonio Terracciano and van der Loos, Matthijs J H M and Vitart, Veronique and V{\"o}lzke, Henry and J{\"u}rgen Wellmann and Lei Yu and Wei Zhao and Allik, J{\"u}ri and John R. Attia and Bandinelli, Stefania and Bastardot, Fran{\c c}ois and Jonathan P. Beauchamp and David A Bennett and Klaus Berger and Laura Bierut and Dorret I Boomsma and B{\"u}ltmann, Ute and Campbell, Harry and Chabris, Christopher F and Cherkas, Lynn and Chung, Mina K and Francesco Cucca and de Andrade, Mariza and Philip L de Jager and De Neve, Jan-Emmanuel and Ian J Deary and George Dedoussis and Deloukas, Panos and Dimitriou, Maria and Gu{\dh}ny Eir{\'\i}ksd{\'o}ttir and Elderson, Martin F and Johan G Eriksson and Jessica Faul and Luigi Ferrucci and Melissa E Garcia and Gr{\"o}nberg, Henrik and Gu{\dh}nason, Vilmundur and Hall, Per and Harris, Juliette M and Tamara B Harris and Nicholas D Hastie and Andrew C Heath and Dena G Hernandez and Hoffmann, Wolfgang and Hofman, Adriaan and Holle, Rolf and Holliday, Elizabeth G and Jouke-Jan Hottenga and Iacono, William G and Illig, Thomas and J{\"a}rvelin, Marjo-Riitta and K{\"a}h{\"o}nen, Mika and Kaprio, Jaakko and Kirkpatrick, Robert M and Kowgier, Matthew and Latvala, Antti and Lenore J Launer and Lawlor, Debbie A and Lehtim{\"a}ki, Terho and Li, Jingmei and Paul Lichtenstein and Lichtner, Peter and David C Liewald and Pamela A F Madden and Patrik K E Magnusson and M{\"a}kinen, Tomi E and Masala, Marco and McGue, Matt and Andres Metspalu and Mielck, Andreas and Michael B Miller and Grant W Montgomery and Mukherjee, Sutapa and Nyholt, Dale R and Ben A Oostra and Palmer, Lyle J and Aarno Palotie and Brenda W J H Penninx and Markus Perola and Peyser, Patricia A and Preisig, Martin and Katri R{\"a}ikk{\"o}nen and Olli T Raitakari and Realo, Anu and Ring, Susan M and Ripatti, Samuli and Fernando Rivadeneira and Rudan, Igor and Rustichini, Aldo and Veikko Salomaa and Sarin, Antti-Pekka and Schlessinger, David and Rodney J Scott and Snieder, Harold and St Pourcain, Beate and John M Starr and Sul, Jae Hoon and Surakka, Ida and Svento, Rauli and Teumer, Alexander and Henning Tiemeier and van Rooij, Frank J A and Van Wagoner, David R and Vartiainen, Erkki and Viikari, Jorma and Vollenweider, Peter and Vonk, Judith M and Waeber, G{\'e}rard and David R Weir and Wichmann, H-Erich and Elisabeth Widen and Gonneke Willemsen and James F Wilson and Alan F Wright and Dalton C Conley and Davey-Smith, George and Lude L Franke and Groenen, Patrick J F and Hofman, Albert and Johannesson, Magnus and Sharon L R Kardia and Krueger, Robert F and David I Laibson and Nicholas G Martin and Meyer, Michelle N and Posthuma, Danielle and A. Roy Thurik and Nicholas J Timpson and Andr{\'e} G Uitterlinden and Cornelia M van Duijn and Peter M Visscher and Daniel J. Benjamin and Cesarini, David and Philipp D Koellinger} }