@article {8618, title = {Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses.}, journal = {Nat Genet}, volume = {48}, year = {2016}, month = {2016 06}, pages = {624-33}, abstract = {

Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (|ρ^| ≈ 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.

}, keywords = {Anxiety Disorders, Bayes Theorem, depression, Genome-Wide Association Study, Humans, Neuroticism, Phenotype, Polymorphism, Single Nucleotide}, issn = {1546-1718}, doi = {10.1038/ng.3552}, author = {Okbay, Aysu and Baselmans, Bart M L and De Neve, Jan-Emmanuel and Turley, Patrick and Nivard, Michel G and Mark Alan Fontana and Meddens, S Fleur W and Richard Karlsson Linn{\'e}r and Cornelius A Rietveld and Derringer, Jaime and Gratten, Jacob and Lee, James J and Liu, Jimmy Z and de Vlaming, Ronald and Ahluwalia, Tarunveer S and Buchwald, Jadwiga and Cavadino, Alana and Frazier-Wood, Alexis C and Furlotte, Nicholas A and Garfield, Victoria and Geisel, Marie Henrike and Gonzalez, Juan R and Haitjema, Saskia and Karlsson, Robert and van der Laan, Sander W and Ladwig, Karl-Heinz and J. Lahti and Sven J van der Lee and Penelope A Lind and Tian Liu and Lindsay K Matteson and Mihailov, Evelin and Michael B Miller and Minica, Camelia C and Ilja M Nolte and Dennis O Mook-Kanamori and van der Most, Peter J and Christopher J Oldmeadow and Qian, Yong and Olli T Raitakari and Rawal, Rajesh and Realo, Anu and Rueedi, Rico and Schmidt, B{\"o}rge and Albert Vernon Smith and Stergiakouli, Evie and Toshiko Tanaka and Kent D Taylor and Wedenoja, Juho and J{\"u}rgen Wellmann and Westra, Harm-Jan and Willems, Sara M and Wei Zhao and Amin, Najaf and Bakshi, Andrew and Patricia A. Boyle and Cherney, Samantha and Cox, Simon R and Gail Davies and Davis, Oliver S P and Ding, Jun and Nese Direk and Eibich, Peter and Emeny, Rebecca T and Fatemifar, Ghazaleh and Jessica Faul and Luigi Ferrucci and Andreas J Forstner and Gieger, Christian and Gupta, Richa and Tamara B Harris and Harris, Juliette M and Holliday, Elizabeth G and Jouke-Jan Hottenga and Philip L de Jager and Marika A Kaakinen and Kajantie, Eero and Karhunen, Ville and Kolcic, Ivana and Kumari, Meena and Lenore J Launer and Lude L Franke and Li-Gao, Ruifang and Koini, Marisa and Loukola, Anu and Marques-Vidal, Pedro and Grant W Montgomery and Mosing, Miriam A and Paternoster, Lavinia and Pattie, Alison and Katja E Petrovic and Pulkki-Raback, Laura and Quaye, Lydia and Katri R{\"a}ikk{\"o}nen and Rudan, Igor and Rodney J Scott and Jennifer A Smith and Angelina R Sutin and Trzaskowski, Maciej and Anna A E Vinkhuyzen and Lei Yu and Zabaneh, Delilah and John R. Attia and David A Bennett and Klaus Berger and Bertram, Lars and Dorret I Boomsma and Snieder, Harold and Chang, Shun-Chiao and Francesco Cucca and Ian J Deary and Cornelia M van Duijn and Johan G Eriksson and B{\"u}ltmann, Ute and Eco J. C. de Geus and Groenen, Patrick J F and Gudnason, Vilmundur and Hansen, Torben and Catharina A Hartman and Haworth, Claire M A and Caroline Hayward and Andrew C Heath and Hinds, David A and Hypp{\"o}nen, Elina and Iacono, William G and J{\"a}rvelin, Marjo-Riitta and J{\"o}ckel, Karl-Heinz and Kaprio, Jaakko and Sharon L R Kardia and Keltikangas-J{\"a}rvinen, Liisa and Kraft, Peter and Laura D Kubzansky and Lehtim{\"a}ki, Terho and Patrik K E Magnusson and Nicholas G Martin and McGue, Matt and Andres Metspalu and Melinda C Mills and de Mutsert, Ren{\'e}e and Oldehinkel, Albertine J and Pasterkamp, Gerard and Nancy L Pedersen and Plomin, Robert and Polasek, Ozren and Power, Christine and Rich, Stephen S and Rosendaal, Frits R and Hester M. den Ruijter and Schlessinger, David and Schmidt, Helena and Svento, Rauli and Schmidt, Reinhold and Alizadeh, Behrooz Z and Thorkild I. A. S{\o}rensen and Timothy Spector and Andrew Steptoe and Antonio Terracciano and A. Roy Thurik and Nicholas J Timpson and Henning Tiemeier and Andr{\'e} G Uitterlinden and Vollenweider, Peter and Wagner, Gert G and David R Weir and Yang, Jian and Dalton C Conley and Hofman, Albert and Johannesson, Magnus and David I Laibson and Sarah E Medland and Meyer, Michelle N and Pickrell, Joseph K and T{\~o}nu Esko and Krueger, Robert F and Jonathan P. Beauchamp and Philipp D Koellinger and Daniel J. Benjamin and Bartels, Meike and Cesarini, David} } @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 {10656, title = {Common genetic variants associated with cognitive performance identified using the proxy-phenotype method.}, journal = {Proc Natl Acad Sci U S A}, volume = {111}, year = {2014}, month = {2014 Sep 23}, pages = {13790-4}, abstract = {

We identify common genetic variants associated with cognitive performance using a two-stage approach, which we call the proxy-phenotype method. First, we conduct a genome-wide association study of educational attainment in a large sample (n = 106,736), which produces a set of 69 education-associated SNPs. Second, using independent samples (n = 24,189), we measure the association of these education-associated SNPs with cognitive performance. Three SNPs (rs1487441, rs7923609, and rs2721173) are significantly associated with cognitive performance after correction for multiple hypothesis testing. In an independent sample of older Americans (n = 8,652), we also show that a polygenic score derived from the education-associated SNPs is associated with memory and absence of dementia. Convergent evidence from a set of bioinformatics analyses implicates four specific genes (KNCMA1, NRXN1, POU2F3, and SCRT). All of these genes are associated with a particular neurotransmitter pathway involved in synaptic plasticity, the main cellular mechanism for learning and memory.

}, keywords = {Cell Adhesion Molecules, Neuronal, Cognition, Female, Humans, Learning, Male, Memory, Multifactorial Inheritance, Nerve Tissue Proteins, Neuronal Plasticity, Octamer Transcription Factors, Polymorphism, Single Nucleotide, Synaptic Transmission}, issn = {1091-6490}, doi = {10.1073/pnas.1404623111}, author = {Cornelius A Rietveld and T{\~o}nu Esko and Gail Davies and Pers, Tune H and Turley, Patrick and Benyamin, Beben and Chabris, Christopher F and Emilsson, Valur and Andrew D Johnson and Lee, James J and Christiaan de Leeuw and Riccardo E Marioni and Sarah E Medland and Michael B Miller and Rostapshova, Olga and Sven J van der Lee and Anna A E Vinkhuyzen and Amin, Najaf and Dalton C Conley and Derringer, Jaime and Cornelia M van Duijn and Fehrmann, Rudolf and Lude L Franke and Edward L Glaeser and Narelle K Hansell and Caroline Hayward and Iacono, William G and Carla A Ibrahim-Verbaas and Vincent Jaddoe and Karjalainen, Juha and David I Laibson and Paul Lichtenstein and David C Liewald and Patrik K E Magnusson and Nicholas G Martin and McGue, Matt and McMahon, George and Nancy L Pedersen and Pinker, Steven and David J Porteous and Posthuma, Danielle and Fernando Rivadeneira and Smith, Blair H and John M Starr and Henning Tiemeier and Nicholas J Timpson and Trzaskowski, Maciej and Andr{\'e} G Uitterlinden and Verhulst, Frank C and Mary E Ward and Margaret J Wright and George Davey Smith and Ian J Deary and Johannesson, Magnus and Plomin, Robert and Peter M Visscher and Daniel J. Benjamin and Cesarini, David and Philipp D Koellinger} } @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} }