TY - JOUR T1 - Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci. JF - Molecular Psychiatry Y1 - 2020 A1 - Erzurumluoglu, A Mesut A1 - Liu, Mengzhen A1 - Jackson, Victoria E A1 - Barnes, Daniel R A1 - Datta, Gargi A1 - Melbourne, Carl A A1 - Young, Robin A1 - Batini, Chiara A1 - Surendran, Praveen A1 - Jiang, Tao A1 - Adnan, Sheikh Daud A1 - Afaq, Saima A1 - Agrawal, Arpana A1 - Altmaier, Elisabeth A1 - Antoniou, Antonis C A1 - Asselbergs, Folkert W A1 - Baumbach, Clemens A1 - Laura Bierut A1 - Bertelsen, Sarah A1 - Boehnke, Michael A1 - Bots, Michiel L A1 - Brazel, David M A1 - Chambers, John C A1 - Chang-Claude, Jenny A1 - Chen, Chu A1 - Corley, Janie A1 - Chou, Yi-Ling A1 - David, Sean P A1 - de Boer, Rudolf A A1 - Christiaan de Leeuw A1 - Joe G Dennis A1 - Dominiczak, Anna F A1 - Dunning, Alison M A1 - Easton, Douglas F A1 - Charles B Eaton A1 - Elliott, Paul A1 - Evangelou, Evangelos A1 - Jessica Faul A1 - Tatiana Foroud A1 - Goate, Alison A1 - Gong, Jian A1 - Hans-Jörgen Grabe A1 - Jeffrey Haessler A1 - Christopher A Haiman A1 - Hallmans, Göran A1 - Anke R Hammerschlag A1 - Sarah E Harris A1 - Andrew T Hattersley A1 - Andrew C Heath A1 - Hsu, Chris A1 - Iacono, William G A1 - Kanoni, Stavroula A1 - Kapoor, Manav A1 - Kaprio, Jaakko A1 - Sharon L R Kardia A1 - Karpe, Fredrik A1 - Kontto, Jukka A1 - Kooner, Jaspal S A1 - Charles Kooperberg A1 - Kuulasmaa, Kari A1 - Laakso, Markku A1 - Lai, Dongbing A1 - Langenberg, Claudia A1 - Le, Nhung A1 - Lettre, Guillaume A1 - Loukola, Anu A1 - Luan, Jian'an A1 - Pamela A F Madden A1 - Mangino, Massimo A1 - Riccardo E Marioni A1 - Marouli, Eirini A1 - Marten, Jonathan A1 - Nicholas G Martin A1 - McGue, Matt A1 - Michailidou, Kyriaki A1 - Mihailov, Evelin A1 - Moayyeri, Alireza A1 - Moitry, Marie A1 - Müller-Nurasyid, Martina A1 - Naheed, Aliya A1 - Nauck, Matthias A1 - Neville, Matthew J A1 - Sune Fallgaard Nielsen A1 - Kari E North A1 - Markus Perola A1 - Pharoah, Paul D P A1 - Pistis, Giorgio A1 - Tinca J Polderman A1 - Posthuma, Danielle A1 - Neil Poulter A1 - Qaiser, Beenish A1 - Rasheed, Asif A1 - Reiner, Alex A1 - Renstrom, Frida A1 - Rice, John A1 - Rohde, Rebecca A1 - Rolandsson, Olov A1 - Nilesh J Samani A1 - Samuel, Maria A1 - Schlessinger, David A1 - H Steven Scholte A1 - Scott, Robert A A1 - Peter Sever A1 - Shao, Yaming A1 - Shrine, Nick A1 - Smith, Jennifer A A1 - John M Starr A1 - Kathleen E Stirrups A1 - Stram, Danielle A1 - Heather M Stringham A1 - Tachmazidou, Ioanna A1 - Tardif, Jean-Claude A1 - Thompson, Deborah J A1 - Hilary A Tindle A1 - Tragante, Vinicius A1 - Trompet, Stella A1 - Turcot, Valérie A1 - Tyrrell, Jessica A1 - Vaartjes, Ilonca A1 - Van Der Leij, Andries R A1 - van der Meer, Peter A1 - Varga, Tibor V A1 - Verweij, Niek A1 - Völzke, Henry A1 - Wareham, Nicholas J A1 - Warren, Helen R A1 - David R Weir A1 - Weiss, Stefan A1 - Wetherill, Leah A1 - Yaghootkar, Hanieh A1 - Yavas, Ersin A1 - Jiang, Yu A1 - Chen, Fang A1 - Zhan, Xiaowei A1 - Zhang, Weihua A1 - Zhao, Wei A1 - Zhao, Wei A1 - Zhou, Kaixin A1 - Amouyel, Philippe A1 - Blankenberg, Stefan A1 - Caulfield, Mark J A1 - Chowdhury, Rajiv A1 - Francesco Cucca A1 - Ian J Deary A1 - Deloukas, Panos A1 - Di Angelantonio, Emanuele A1 - Marco M Ferrario A1 - Ferrières, Jean A1 - Franks, Paul W A1 - Timothy M Frayling A1 - Frossard, Philippe A1 - Hall, Ian P A1 - Caroline Hayward A1 - Jansson, Jan-Håkan A1 - Jukema, J Wouter A1 - Kee, Frank A1 - Männistö, Satu A1 - Andres Metspalu A1 - Munroe, Patricia B A1 - Børge G Nordestgaard A1 - Palmer, Colin N A A1 - Veikko Salomaa A1 - Sattar, Naveed A1 - Timothy Spector A1 - David P Strachan A1 - van der Harst, Pim A1 - Zeggini, Eleftheria A1 - Saleheen, Danish A1 - Adam S Butterworth A1 - Wain, Louise V A1 - Gonçalo R Abecasis A1 - Danesh, John A1 - Tobin, Martin D A1 - Scott Vrieze A1 - Liu, Dajiang J A1 - Howson, Joanna M M KW - Biological Specimen Banks KW - Databases, Factual KW - Europe KW - Exome KW - Female KW - Genetic Loci KW - Humans KW - Male KW - Polymorphism, Single Nucleotide KW - Smoking KW - United Kingdom AB -

Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P < 5 × 10 in either analysis were taken forward for replication in up to 275,596 independent participants from UK Biobank. Lastly, a meta-analysis of the discovery and replication studies was performed. Sixteen SNVs were associated with at least one of the smoking behaviour traits (P < 5 × 10) in the discovery samples. Ten novel SNVs, including rs12616219 near TMEM182, were followed-up and five of them (rs462779 in REV3L, rs12780116 in CNNM2, rs1190736 in GPR101, rs11539157 in PJA1, and rs12616219 near TMEM182) replicated at a Bonferroni significance threshold (P < 4.5 × 10) with consistent direction of effect. A further 35 SNVs were associated with smoking behaviour traits in the discovery plus replication meta-analysis (up to 622,409 participants) including a rare SNV, rs150493199, in CCDC141 and two low-frequency SNVs in CEP350 and HDGFRP2. Functional follow-up implied that decreased expression of REV3L may lower the probability of smoking initiation. The novel loci will facilitate understanding the genetic aetiology of smoking behaviour and may lead to the identification of potential drug targets for smoking prevention and/or cessation.

VL - 25 IS - 10 ER - TY - JOUR T1 - Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use. JF - Nature Genetics Y1 - 2019 A1 - Liu, Mengzhen A1 - Jiang, Yu A1 - Wedow, Robbee A1 - Li, Yue A1 - Brazel, David M A1 - Chen, Fang A1 - Datta, Gargi A1 - Davila-Velderrain, Jose A1 - McGuire, Daniel A1 - Tian, Chao A1 - Zhan, Xiaowei A1 - Choquet, Hélène A1 - Docherty, Anna R A1 - Jessica Faul A1 - Foerster, Johanna R A1 - Fritsche, Lars G A1 - Gabrielsen, Maiken Elvestad A1 - Gordon, Scott D A1 - Jeffrey Haessler A1 - Jouke-Jan Hottenga A1 - Huang, Hongyan A1 - Jang, Seon-Kyeong A1 - Philip R Jansen A1 - Ling, Yueh A1 - Mägi, Reedik A1 - Matoba, Nana A1 - McMahon, George A1 - Mulas, Antonella A1 - Orrù, Valeria A1 - Palviainen, Teemu A1 - Anita Pandit A1 - Reginsson, Gunnar W A1 - Skogholt, Anne Heidi A1 - Smith, Jennifer A A1 - Taylor, Amy E A1 - Turman, Constance A1 - Gonneke Willemsen A1 - Young, Hannah A1 - Young, Kendra A A1 - Zajac, Gregory J M A1 - Zhao, Wei A1 - Zhou, Wei A1 - Bjornsdottir, Gyda A1 - Boardman, Jason D A1 - Boehnke, Michael A1 - Dorret I Boomsma A1 - Chen, Chu A1 - Francesco Cucca A1 - Davies, Gareth E A1 - Charles B Eaton A1 - Ehringer, Marissa A A1 - Tõnu Esko A1 - Fiorillo, Edoardo A1 - Gillespie, Nathan A A1 - Gudbjartsson, Daniel F A1 - Haller, Toomas A1 - Kathleen Mullan Harris A1 - Andrew C Heath A1 - Hewitt, John K A1 - Hickie, Ian B A1 - Hokanson, John E A1 - Hopfer, Christian J A1 - Hunter, David J A1 - Iacono, William G A1 - Johnson, Eric O A1 - Kamatani, Yoichiro A1 - Sharon L R Kardia A1 - Matthew C Keller A1 - Kellis, Manolis A1 - Charles Kooperberg A1 - Kraft, Peter A1 - Krauter, Kenneth S A1 - Laakso, Markku A1 - Penelope A Lind A1 - Loukola, Anu A1 - Lutz, Sharon M A1 - Pamela A F Madden A1 - Nicholas G Martin A1 - McGue, Matt A1 - Matthew B McQueen A1 - Sarah E Medland A1 - Andres Metspalu A1 - Mohlke, Karen L A1 - Nielsen, Jonas B A1 - Okada, Yukinori A1 - Peters, Ulrike A1 - Tinca J Polderman A1 - Posthuma, Danielle A1 - Reiner, Alexander P A1 - Rice, John P A1 - Rimm, Eric A1 - Rose, Richard J A1 - Runarsdottir, Valgerdur A1 - Stallings, Michael C A1 - Stančáková, Alena A1 - Stefansson, Hreinn A1 - Thai, Khanh K A1 - Hilary A Tindle A1 - Tyrfingsson, Thorarinn A1 - Wall, Tamara L A1 - David R Weir A1 - Weisner, Constance A1 - Whitfield, John B A1 - Winsvold, Bendik Slagsvold A1 - Yin, Jie A1 - Zuccolo, Luisa A1 - Laura Bierut A1 - Hveem, Kristian A1 - Lee, James J A1 - Munafò, Marcus R A1 - Saccone, Nancy L A1 - Willer, Cristen J A1 - Marilyn C Cornelis A1 - David, Sean P A1 - Hinds, David A A1 - Jorgenson, Eric A1 - Kaprio, Jaakko A1 - Stitzel, Jerry A A1 - Stefansson, Kari A1 - Thorgeirsson, Thorgeir E A1 - Gonçalo R Abecasis A1 - Liu, Dajiang J A1 - Scott Vrieze KW - Alcohol Drinking KW - Female KW - Genetic Variation KW - Genome-Wide Association Study KW - Humans KW - Male KW - Middle Aged KW - Phenotype KW - Risk KW - Smoking KW - Tobacco KW - Tobacco Use Disorder AB -

Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders. They are heritable and etiologically related behaviors that have been resistant to gene discovery efforts. In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures.

VL - 51 IS - 2 ER - TY - JOUR T1 - Exome Chip Meta-analysis Fine Maps Causal Variants and Elucidates the Genetic Architecture of Rare Coding Variants in Smoking and Alcohol Use. JF - Biological Psychiatry Y1 - 2019 A1 - Brazel, David M A1 - Jiang, Yu A1 - Hughey, Jordan M A1 - Turcot, Valérie A1 - Zhan, Xiaowei A1 - Gong, Jian A1 - Batini, Chiara A1 - Weissenkampen, J Dylan A1 - Liu, Mengzhen A1 - Barnes, Daniel R A1 - Bertelsen, Sarah A1 - Chou, Yi-Ling A1 - Erzurumluoglu, A Mesut A1 - Jessica Faul A1 - Jeffrey Haessler A1 - Anke R Hammerschlag A1 - Hsu, Chris A1 - Kapoor, Manav A1 - Lai, Dongbing A1 - Le, Nhung A1 - Christiaan de Leeuw A1 - Loukola, Anu A1 - Mangino, Massimo A1 - Melbourne, Carl A A1 - Pistis, Giorgio A1 - Qaiser, Beenish A1 - Rohde, Rebecca A1 - Shao, Yaming A1 - Heather M Stringham A1 - Wetherill, Leah A1 - Zhao, Wei A1 - Agrawal, Arpana A1 - Laura Bierut A1 - Chen, Chu A1 - Charles B Eaton A1 - Goate, Alison A1 - Christopher A Haiman A1 - Andrew C Heath A1 - Iacono, William G A1 - Nicholas G Martin A1 - Tinca J Polderman A1 - Reiner, Alex A1 - Rice, John A1 - Schlessinger, David A1 - H Steven Scholte A1 - Smith, Jennifer A A1 - Tardif, Jean-Claude A1 - Hilary A Tindle A1 - Van Der Leij, Andries R A1 - Boehnke, Michael A1 - Chang-Claude, Jenny A1 - Francesco Cucca A1 - David, Sean P A1 - Tatiana Foroud A1 - Howson, Joanna M M A1 - Sharon L R Kardia A1 - Charles Kooperberg A1 - Laakso, Markku A1 - Lettre, Guillaume A1 - Pamela A F Madden A1 - McGue, Matt A1 - Kari E North A1 - Posthuma, Danielle A1 - Timothy Spector A1 - Stram, Daniel A1 - Tobin, Martin D A1 - David R Weir A1 - Kaprio, Jaakko A1 - Gonçalo R Abecasis A1 - Liu, Dajiang J A1 - Scott Vrieze KW - Alcohol Drinking KW - Databases, Genetic KW - Exome KW - Genetic Predisposition to Disease KW - Genetic Variation KW - Genome-Wide Association Study KW - Genotype KW - Humans KW - Oligonucleotide Array Sequence Analysis KW - Phenotype KW - Polymorphism, Single Nucleotide KW - Smoking AB -

BACKGROUND: Smoking and alcohol use have been associated with common genetic variants in multiple loci. Rare variants within these loci hold promise in the identification of biological mechanisms in substance use. Exome arrays and genotype imputation can now efficiently genotype rare nonsynonymous and loss of function variants. Such variants are expected to have deleterious functional consequences and to contribute to disease risk.

METHODS: We analyzed ∼250,000 rare variants from 16 independent studies genotyped with exome arrays and augmented this dataset with imputed data from the UK Biobank. Associations were tested for five phenotypes: cigarettes per day, pack-years, smoking initiation, age of smoking initiation, and alcoholic drinks per week. We conducted stratified heritability analyses, single-variant tests, and gene-based burden tests of nonsynonymous/loss-of-function coding variants. We performed a novel fine-mapping analysis to winnow the number of putative causal variants within associated loci.

RESULTS: Meta-analytic sample sizes ranged from 152,348 to 433,216, depending on the phenotype. Rare coding variation explained 1.1% to 2.2% of phenotypic variance, reflecting 11% to 18% of the total single nucleotide polymorphism heritability of these phenotypes. We identified 171 genome-wide associated loci across all phenotypes. Fine mapping identified putative causal variants with double base-pair resolution at 24 of these loci, and between three and 10 variants for 65 loci. Twenty loci contained rare coding variants in the 95% credible intervals.

CONCLUSIONS: Rare coding variation significantly contributes to the heritability of smoking and alcohol use. Fine-mapping genome-wide association study loci identifies specific variants contributing to the biological etiology of substance use behavior.

VL - 85 IS - 11 ER - TY - JOUR T1 - Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence JF - Nature Genetics Y1 - 2018 A1 - Savage, Jeanne E. A1 - Philip R Jansen A1 - Stringer, Sven A1 - Watanabe, Kyoko A1 - Bryois, Julien A1 - Christiaan de Leeuw A1 - Nagel, Mats A1 - Awasthi, Swapnil A1 - Barr, Peter B. A1 - Coleman, Jonathan R. I. A1 - Grasby, Katrina L. A1 - Anke R Hammerschlag A1 - Kaminski, Jakob A. A1 - Karlsson, Robert A1 - Krapohl, Eva A1 - Lam, Max A1 - Nygaard, Marianne A1 - Chandra A Reynolds A1 - Joey W Trampush A1 - Young, Hannah A1 - Zabaneh, Delilah A1 - Hägg, Sara A1 - Narelle K Hansell A1 - Ida Karlsson A1 - Linnarsson, Sten A1 - Grant W Montgomery A1 - Muñoz-Manchado, Ana B. A1 - Quinlan, Erin B. A1 - Schumann, Gunter A1 - Skene, Nathan G. A1 - Webb, Bradley T. A1 - White, Tonya A1 - Dan E Arking A1 - Avramopoulos, Dimitrios A1 - Robert M Bilder A1 - Bitsios, Panos A1 - Katherine E Burdick A1 - Tyrone D. Cannon A1 - Chiba-Falek, Ornit A1 - Christoforou, Andrea A1 - Elizabeth T. Cirulli A1 - Congdon, Eliza A1 - Corvin, Aiden A1 - Gail Davies A1 - Ian J Deary A1 - DeRosse, Pamela A1 - Dickinson, Dwight A1 - Djurovic, Srdjan A1 - Donohoe, Gary A1 - Conley, Emily Drabant A1 - Johan G Eriksson A1 - Espeseth, Thomas A1 - Nelson A. Freimer A1 - Giakoumaki, Stella A1 - Giegling, Ina A1 - Gill, Michael A1 - David C. Glahn A1 - Ahmad R Hariri A1 - Hatzimanolis, Alex A1 - Matthew C Keller A1 - Knowles, Emma A1 - Koltai, Deborah A1 - Konte, Bettina A1 - Lahti, Jari A1 - Stephanie Le Hellard A1 - Lencz, Todd A1 - David C Liewald A1 - London, Edythe A1 - Astri J Lundervold A1 - Anil K. Malhotra A1 - Melle, Ingrid A1 - Morris, Derek A1 - Anna C Need A1 - William E R Ollier A1 - Aarno Palotie A1 - Payton, Antony A1 - Pendleton, Neil A1 - Russell A Poldrack A1 - Katri Räikkönen A1 - Reinvang, Ivar A1 - Roussos, Panos A1 - Rujescu, Dan A1 - Fred W Sabb A1 - Matthew A Scult A1 - Smeland, Olav B. A1 - Smyrnis, Nikolaos A1 - John M Starr A1 - Vidar M Steen A1 - Nikos C Stefanis A1 - Richard E Straub A1 - Sundet, Kjetil A1 - Henning Tiemeier A1 - Aristotle N Voineskos A1 - Daniel R Weinberger A1 - Elisabeth Widen A1 - Yu, Jin A1 - Gonçalo R Abecasis A1 - Andreassen, Ole A. A1 - Breen, Gerome A1 - Christiansen, Lene A1 - Debrabant, Birgit A1 - Danielle M. Dick A1 - Heinz, Andreas A1 - Hjerling-Leffler, Jens A1 - Mohammed Arfan Ikram A1 - Kendler, Kenneth S. A1 - Nicholas G Martin A1 - Sarah E Medland A1 - Nancy L Pedersen A1 - Plomin, Robert A1 - Tinca J Polderman A1 - Ripke, Stephan A1 - van der Sluis, Sophie A1 - Patrick F. Sullivan A1 - Scott Vrieze A1 - Margaret J Wright A1 - Posthuma, Danielle KW - Genome-Wide Association Study KW - Intelligence KW - Meta-analyses AB - Intelligence is highly heritable1 and a major determinant of human health and well-being2. Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence3-7, but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders. VL - 50 UR - http://www.nature.com/articles/s41588-018-0152-6http://www.nature.com/articles/s41588-018-0152-6.pdfhttp://www.nature.com/articles/s41588-018-0152-6http://www.nature.com/articles/s41588-018-0152-6.pdf IS - 7 JO - Nat Genet ER - TY - JOUR T1 - Rare and low-frequency coding variants alter human adult height. JF - Nature Y1 - 2017 A1 - Marouli, Eirini A1 - Graff, Mariaelisa A1 - Medina-Gomez, Carolina A1 - Ken Sin Lo A1 - Andrew R Wood A1 - Kjaer, Troels R A1 - Fine, Rebecca S A1 - Lu, Yingchang A1 - Schurmann, Claudia A1 - Highland, Heather M A1 - Rüeger, Sina A1 - Thorleifsson, Gudmar A1 - Justice, Anne E A1 - Lamparter, David A1 - Kathleen E Stirrups A1 - Turcot, Valérie A1 - Young, Kristin L A1 - Thomas W Winkler A1 - Tõnu Esko A1 - Karaderi, Tugce A1 - Locke, Adam E A1 - Masca, Nicholas G D A1 - Ng, Maggie C Y A1 - Mudgal, Poorva A1 - Rivas, Manuel A A1 - Vedantam, Sailaja A1 - Mahajan, Anubha A1 - Guo, Xiuqing A1 - Gonçalo R Abecasis A1 - Aben, Katja K A1 - Adair, Linda S A1 - Alam, Dewan S A1 - Albrecht, Eva A1 - Allin, Kristine H A1 - Matthew A. Allison A1 - Amouyel, Philippe A1 - Appel, Emil V A1 - Arveiler, Dominique A1 - Asselbergs, Folkert W A1 - Auer, Paul L A1 - Balkau, Beverley A1 - Banas, Bernhard A1 - Bang, Lia E A1 - Benn, Marianne A1 - Bergmann, Sven A1 - Bielak, Lawrence F A1 - Blüher, Matthias A1 - Boeing, Heiner A1 - Boerwinkle, Eric A1 - Böger, Carsten A A1 - Bonnycastle, Lori L A1 - Bork-Jensen, Jette A1 - Bots, Michiel L A1 - Erwin P Bottinger A1 - Bowden, Donald W A1 - Brandslund, Ivan A1 - Breen, Gerome A1 - Brilliant, Murray H A1 - Broer, Linda A1 - Burt, Amber A A1 - Adam S Butterworth A1 - Carey, David J A1 - Caulfield, Mark J A1 - Chambers, John C A1 - Daniel I Chasman A1 - Yii-Der I Chen A1 - Chowdhury, Rajiv A1 - Cramer Christensen A1 - Chu, Audrey Y A1 - Cocca, Massimiliano A1 - Collins, Francis S A1 - Cook, James P A1 - Corley, Janie A1 - Jordi Corominas Galbany A1 - Cox, Amanda J A1 - Cuellar-Partida, Gabriel A1 - Danesh, John A1 - Gail Davies A1 - de Bakker, Paul I W A1 - de Borst, Gert J A1 - de Denus, Simon A1 - de Groot, Mark C H A1 - de Mutsert, Renée A1 - Ian J Deary A1 - George Dedoussis A1 - Ellen W Demerath A1 - Anneke I den Hollander A1 - Joe G Dennis A1 - Di Angelantonio, Emanuele A1 - Drenos, Fotios A1 - Du, Mengmeng A1 - Dunning, Alison M A1 - Easton, Douglas F A1 - Ebeling, Tapani A1 - Edwards, Todd L A1 - Ellinor, Patrick T A1 - Elliott, Paul A1 - Evangelou, Evangelos A1 - Farmaki, Aliki-Eleni A1 - Jessica Faul A1 - Feitosa, Mary F A1 - Feng, Shuang A1 - Ferrannini, Ele A1 - Marco M Ferrario A1 - Ferrières, Jean A1 - Florez, Jose C A1 - Ford, Ian A1 - Myriam Fornage A1 - Franks, Paul W A1 - Frikke-Schmidt, Ruth A1 - Galesloot, Tessel E A1 - Gan, Wei A1 - Gandin, Ilaria A1 - Paolo P. Gasparini A1 - Giedraitis, Vilmantas A1 - Giri, Ayush A1 - Giorgia G Girotto A1 - Gordon, Scott D A1 - Gordon-Larsen, Penny A1 - Gorski, Mathias A1 - Grarup, Niels A1 - Grove, Megan L A1 - Gudnason, Vilmundur A1 - Gustafsson, Stefan A1 - Hansen, Torben A1 - Kathleen Mullan Harris A1 - Tamara B Harris A1 - Andrew T Hattersley A1 - Caroline Hayward A1 - He, Liang A1 - Iris M Heid A1 - Heikkilä, Kauko A1 - Helgeland, Øyvind A1 - Hernesniemi, Jussi A1 - Hewitt, Alex W A1 - Lynne J Hocking A1 - Hollensted, Mette A1 - Oddgeir L Holmen A1 - Hovingh, G Kees A1 - Howson, Joanna M M A1 - Hoyng, Carel B A1 - Huang, Paul L A1 - Hveem, Kristian A1 - Mohammed Arfan Ikram A1 - Ingelsson, Erik A1 - Jackson, Anne U A1 - Jansson, Jan-Håkan A1 - Jarvik, Gail P A1 - Jensen, Gorm B A1 - Jhun, Min A A1 - Jia, Yucheng A1 - Jiang, Xuejuan A1 - Johansson, Stefan A1 - Jørgensen, Marit E A1 - Jørgensen, Torben A1 - Jousilahti, Pekka A1 - Jukema, J Wouter A1 - Kahali, Bratati A1 - Kahn, René S A1 - Kähönen, Mika A1 - Kamstrup, Pia R A1 - Kanoni, Stavroula A1 - Kaprio, Jaakko A1 - Karaleftheri, Maria A1 - Sharon L R Kardia A1 - Karpe, Fredrik A1 - Kee, Frank A1 - Keeman, Renske A1 - Lambertus A Kiemeney A1 - Kitajima, Hidetoshi A1 - Kluivers, Kirsten B A1 - Kocher, Thomas A1 - Komulainen, Pirjo A1 - Kontto, Jukka A1 - Kooner, Jaspal S A1 - Charles Kooperberg A1 - Kovacs, Peter A1 - Kriebel, Jennifer A1 - Kuivaniemi, Helena A1 - Küry, Sébastien A1 - Kuusisto, Johanna A1 - La Bianca, Martina A1 - Laakso, Markku A1 - Lakka, Timo A A1 - Lange, Ethan M A1 - Leslie A Lange A1 - Langefeld, Carl D A1 - Langenberg, Claudia A1 - Eric B Larson A1 - Lee, I-Te A1 - Lehtimäki, Terho A1 - Lewis, Cora E A1 - Li, Huaixing A1 - Li, Jin A1 - Li-Gao, Ruifang A1 - Lin, Honghuang A1 - Lin, Li-An A1 - Lin, Xu A1 - Lars Lind A1 - Lindström, Jaana A1 - Linneberg, Allan A1 - Liu, Yeheng A1 - Yongmei Liu A1 - Lophatananon, Artitaya A1 - Luan, Jian'an A1 - Lubitz, Steven A A1 - Lyytikäinen, Leo-Pekka A1 - Mackey, David A A1 - Pamela A F Madden A1 - Alisa Manning A1 - Männistö, Satu A1 - Marenne, Gaëlle A1 - Marten, Jonathan A1 - Nicholas G Martin A1 - Mazul, Angela L A1 - Meidtner, Karina A1 - Andres Metspalu A1 - Mitchell, Paul A1 - Mohlke, Karen L A1 - Dennis O Mook-Kanamori A1 - Morgan, Anna A1 - Morris, Andrew D A1 - Morris, Andrew P A1 - Müller-Nurasyid, Martina A1 - Munroe, Patricia B A1 - Michael A Nalls A1 - Nauck, Matthias A1 - Nelson, Christopher P A1 - Neville, Matt A1 - Sune Fallgaard Nielsen A1 - Nikus, Kjell A1 - Njølstad, Pål R A1 - Børge G Nordestgaard A1 - Ntalla, Ioanna A1 - Jeff O'Connell A1 - Oksa, Heikki A1 - Loes M Olde Loohuis A1 - Ophoff, Roel A A1 - Owen, Katharine R A1 - Packard, Chris J A1 - Padmanabhan, Sandosh A1 - Palmer, Colin N A A1 - Pasterkamp, Gerard A1 - Patel, Aniruddh P A1 - Pattie, Alison A1 - Pedersen, Oluf A1 - Peissig, Peggy L A1 - Peloso, Gina M A1 - Pennell, Craig E A1 - Markus Perola A1 - Perry, James A A1 - Perry, John R B A1 - Person, Thomas N A1 - Pirie, Ailith A1 - Polasek, Ozren A1 - Posthuma, Danielle A1 - Olli T Raitakari A1 - Rasheed, Asif A1 - Rauramaa, Rainer A1 - Reilly, Dermot F A1 - Reiner, Alex P A1 - Renstrom, Frida A1 - Ridker, Paul M A1 - Rioux, John D A1 - Neil R Robertson A1 - Robino, Antonietta A1 - Rolandsson, Olov A1 - Rudan, Igor A1 - Ruth, Katherine S A1 - Saleheen, Danish A1 - Veikko Salomaa A1 - Nilesh J Samani A1 - Sandow, Kevin A1 - Sapkota, Yadav A1 - Sattar, Naveed A1 - Schmidt, Marjanka K A1 - Schreiner, Pamela J A1 - Schulze, Matthias B A1 - Scott, Robert A A1 - Segura-Lepe, Marcelo P A1 - Svati H Shah A1 - Sim, Xueling A1 - Sivapalaratnam, Suthesh A1 - Small, Kerrin S A1 - Albert Vernon Smith A1 - Jennifer A Smith A1 - Southam, Lorraine A1 - Timothy Spector A1 - Elizabeth K Speliotes A1 - John M Starr A1 - Steinthorsdottir, Valgerdur A1 - Heather M Stringham A1 - Stumvoll, Michael A1 - Surendran, Praveen A1 - 't Hart, Leen M A1 - Tansey, Katherine E A1 - Tardif, Jean-Claude A1 - Kent D Taylor A1 - Teumer, Alexander A1 - Thompson, Deborah J A1 - Thorsteinsdottir, Unnur A1 - Thuesen, Betina H A1 - Tönjes, Anke A1 - Tromp, Gerard A1 - Trompet, Stella A1 - Tsafantakis, Emmanouil A1 - Tuomilehto, Jaakko A1 - Tybjaerg-Hansen, Anne A1 - Tyrer, Jonathan P A1 - Uher, Rudolf A1 - André G Uitterlinden A1 - Ulivi, Sheila A1 - van der Laan, Sander W A1 - Van Der Leij, Andries R A1 - Cornelia M van Duijn A1 - van Schoor, Natasja M A1 - van Setten, Jessica A1 - Varbo, Anette A1 - Varga, Tibor V A1 - Varma, Rohit A1 - Digna R Velez Edwards A1 - Vermeulen, Sita H A1 - Vestergaard, Henrik A1 - Vitart, Veronique A1 - Vogt, Thomas F A1 - Vozzi, Diego A1 - Walker, Mark A1 - Wang, Feijie A1 - Wang, Carol A A1 - Wang, Shuai A1 - Wang, Yiqin A1 - Wareham, Nicholas J A1 - Warren, Helen R A1 - Wessel, Jennifer A1 - Willems, Sara M A1 - Wilson, James G A1 - Daniel Witte A1 - Woods, Michael O A1 - Wu, Ying A1 - Yaghootkar, Hanieh A1 - Yao, Jie A1 - Yao, Pang A1 - Laura M Yerges-Armstrong A1 - Young, Robin A1 - Zeggini, Eleftheria A1 - Zhan, Xiaowei A1 - Zhang, Weihua A1 - Jing Hua Zhao A1 - Wei Zhao A1 - Wei Zhao A1 - Zheng, He A1 - Zhou, Wei A1 - Rotter, Jerome I A1 - Boehnke, Michael A1 - Kathiresan, Sekar A1 - McCarthy, Mark I A1 - Willer, Cristen J A1 - Stefansson, Kari A1 - Ingrid B Borecki A1 - Liu, Dajiang J A1 - Kari E North A1 - Heard-Costa, Nancy L A1 - Pers, Tune H A1 - Lindgren, Cecilia M A1 - Oxvig, Claus A1 - Kutalik, Zoltán A1 - Fernando Rivadeneira A1 - Ruth J F Loos A1 - Timothy M Frayling A1 - Joel N Hirschhron A1 - Deloukas, Panos A1 - Lettre, Guillaume AB -

Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height-increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.

VL - 542 IS - 7640 U1 - http://www.ncbi.nlm.nih.gov/pubmed/28146470?dopt=Abstract ER - TY - JOUR T1 - Genome-wide association study identifies 74 loci associated with educational attainment. JF - Nature Y1 - 2016 A1 - Okbay, Aysu A1 - Jonathan P. Beauchamp A1 - Mark Alan Fontana A1 - Lee, James J A1 - Pers, Tune H A1 - Cornelius A Rietveld A1 - Turley, Patrick A1 - Chen, Guo-Bo A1 - Emilsson, Valur A1 - Meddens, S Fleur W A1 - Oskarsson, Sven A1 - Pickrell, Joseph K A1 - Thom, Kevin A1 - Pascal N Timshel A1 - de Vlaming, Ronald A1 - Abdel Abdellaoui A1 - Ahluwalia, Tarunveer S A1 - Bacelis, Jonas A1 - Baumbach, Clemens A1 - Bjornsdottir, Gyda A1 - Brandsma, Johannes H A1 - Maria Pina Concas A1 - Derringer, Jaime A1 - Furlotte, Nicholas A A1 - Galesloot, Tessel E A1 - Giorgia G Girotto A1 - Gupta, Richa A1 - Hall, Leanne M A1 - Sarah E Harris A1 - Edith Hofer A1 - Horikoshi, Momoko A1 - Huffman, Jennifer E A1 - Kaasik, Kadri A1 - Ioanna Panagiota Kalafati A1 - Karlsson, Robert A1 - Kong, Augustine A1 - Lahti, Jari A1 - Sven J van der Lee A1 - Christiaan de Leeuw A1 - Penelope A Lind A1 - Lindgren, Karl-Oskar A1 - Tian Liu A1 - Mangino, Massimo A1 - Marten, Jonathan A1 - Mihailov, Evelin A1 - Michael B Miller A1 - van der Most, Peter J A1 - Christopher J Oldmeadow A1 - Payton, Antony A1 - Pervjakova, Natalia A1 - Wouter J Peyrot A1 - Qian, Yong A1 - Olli T Raitakari A1 - Rueedi, Rico A1 - Salvi, Erika A1 - Schmidt, Börge A1 - Schraut, Katharina E A1 - Jianxin Shi A1 - Albert Vernon Smith A1 - Poot, Raymond A A1 - St Pourcain, Beate A1 - Teumer, Alexander A1 - Thorleifsson, Gudmar A1 - Verweij, Niek A1 - Vuckovic, Dragana A1 - Jürgen Wellmann A1 - Westra, Harm-Jan A1 - Yang, Jingyun A1 - Wei Zhao A1 - Zhihong Zhu A1 - Alizadeh, Behrooz Z A1 - Amin, Najaf A1 - Bakshi, Andrew A1 - Baumeister, Sebastian E A1 - Biino, Ginevra A1 - Bønnelykke, Klaus A1 - Patricia A. Boyle A1 - Campbell, Harry A1 - Cappuccio, Francesco P A1 - Gail Davies A1 - De Neve, Jan-Emmanuel A1 - Deloukas, Panos A1 - Demuth, Ilja A1 - Ding, Jun A1 - Eibich, Peter A1 - Eisele, Lewin A1 - Eklund, Niina A1 - Jessica Faul A1 - Feitosa, Mary F A1 - Andreas J Forstner A1 - Gandin, Ilaria A1 - Gunnarsson, Bjarni A1 - Halldórsson, Bjarni V A1 - Tamara B Harris A1 - Andrew C Heath A1 - Lynne J Hocking A1 - Holliday, Elizabeth G A1 - Homuth, Georg A1 - Horan, Michael A A1 - Jouke-Jan Hottenga A1 - Philip L de Jager A1 - Joshi, Peter K A1 - Jugessur, Astanand A1 - Marika A Kaakinen A1 - Kähönen, Mika A1 - Kanoni, Stavroula A1 - Keltigangas-Järvinen, Liisa A1 - Lambertus A Kiemeney A1 - Kolcic, Ivana A1 - Koskinen, Seppo A1 - Kraja, Aldi T A1 - Kroh, Martin A1 - Kutalik, Zoltán A1 - Latvala, Antti A1 - Lenore J Launer A1 - Lebreton, Maël P A1 - Douglas F Levinson A1 - Paul Lichtenstein A1 - Lichtner, Peter A1 - David C Liewald A1 - Loukola, Anu A1 - Pamela A F Madden A1 - Mägi, Reedik A1 - Mäki-Opas, Tomi A1 - Riccardo E Marioni A1 - Marques-Vidal, Pedro A1 - Meddens, Gerardus A A1 - McMahon, George A1 - Meisinger, Christa A1 - Meitinger, Thomas A1 - Milaneschi, Yusplitri A1 - Lili Milani A1 - Grant W Montgomery A1 - Myhre, Ronny A1 - Nelson, Christopher P A1 - Nyholt, Dale R A1 - William E R Ollier A1 - Aarno Palotie A1 - Paternoster, Lavinia A1 - Nancy L Pedersen A1 - Katja E Petrovic A1 - David J Porteous A1 - Katri Räikkönen A1 - Ring, Susan M A1 - Robino, Antonietta A1 - Rostapshova, Olga A1 - Rudan, Igor A1 - Rustichini, Aldo A1 - Veikko Salomaa A1 - Sanders, Alan R A1 - Sarin, Antti-Pekka A1 - Schmidt, Helena A1 - Rodney J Scott A1 - Smith, Blair H A1 - Jennifer A Smith A1 - Staessen, Jan A A1 - Steinhagen-Thiessen, Elisabeth A1 - Strauch, Konstantin A1 - Antonio Terracciano A1 - Tobin, Martin D A1 - Ulivi, Sheila A1 - Vaccargiu, Simona A1 - Quaye, Lydia A1 - van Rooij, Frank J A A1 - Venturini, Cristina A1 - Anna A E Vinkhuyzen A1 - Völker, Uwe A1 - Völzke, Henry A1 - Vonk, Judith M A1 - Vozzi, Diego A1 - Waage, Johannes A1 - Erin B Ware A1 - Gonneke Willemsen A1 - John R. Attia A1 - David A Bennett A1 - Klaus Berger A1 - Bertram, Lars A1 - Bisgaard, Hans A1 - Dorret I Boomsma A1 - Ingrid B Borecki A1 - Bültmann, Ute A1 - Chabris, Christopher F A1 - Francesco Cucca A1 - Cusi, Daniele A1 - Ian J Deary A1 - George Dedoussis A1 - Cornelia M van Duijn A1 - Johan G Eriksson A1 - Franke, Barbara A1 - Lude L Franke A1 - Paolo P. Gasparini A1 - Gejman, Pablo V A1 - Gieger, Christian A1 - Hans-Jörgen Grabe A1 - Gratten, Jacob A1 - Groenen, Patrick J F A1 - Gudnason, Vilmundur A1 - van der Harst, Pim A1 - Caroline Hayward A1 - Hinds, David A A1 - Hoffmann, Wolfgang A1 - Hyppönen, Elina A1 - Iacono, William G A1 - Jacobsson, Bo A1 - Järvelin, Marjo-Riitta A1 - Jöckel, Karl-Heinz A1 - Kaprio, Jaakko A1 - Sharon L R Kardia A1 - Lehtimäki, Terho A1 - Lehrer, Steven F A1 - Patrik K E Magnusson A1 - Nicholas G Martin A1 - McGue, Matt A1 - Andres Metspalu A1 - Pendleton, Neil A1 - Brenda W J H Penninx A1 - Markus Perola A1 - Nicola Pirastu A1 - Pirastu, Mario A1 - Polasek, Ozren A1 - Posthuma, Danielle A1 - Power, Christine A1 - Province, Michael A A1 - Nilesh J Samani A1 - Schlessinger, David A1 - Schmidt, Reinhold A1 - Thorkild I. A. Sørensen A1 - Timothy Spector A1 - Stefansson, Kari A1 - Thorsteinsdottir, Unnur A1 - A. Roy Thurik A1 - Nicholas J Timpson A1 - Henning Tiemeier A1 - Tung, Joyce Y A1 - André G Uitterlinden A1 - Vitart, Veronique A1 - Vollenweider, Peter A1 - David R Weir A1 - James F Wilson A1 - Alan F Wright A1 - Dalton C Conley A1 - Krueger, Robert F A1 - George Davey Smith A1 - Hofman, Albert A1 - David I Laibson A1 - Sarah E Medland A1 - Meyer, Michelle N A1 - Yang, Jian A1 - Johannesson, Magnus A1 - Peter M Visscher A1 - Tõnu Esko A1 - Philipp D Koellinger A1 - Cesarini, David A1 - Daniel J. Benjamin KW - Alzheimer's disease KW - Bipolar Disorder KW - Cognitive Ability KW - Education KW - Fetus KW - Genome-Wide Association Study KW - Humans KW - Molecular Sequence Annotation KW - Polymorphism, Single Nucleotide KW - Schizophrenia KW - United Kingdom AB -

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.

VL - 533 IS - 7604 U1 - http://www.ncbi.nlm.nih.gov/pubmed/27225129?dopt=Abstract ER - TY - JOUR T1 - Common genetic variants associated with cognitive performance identified using the proxy-phenotype method. JF - Proc Natl Acad Sci U S A Y1 - 2014 A1 - Cornelius A Rietveld A1 - Tõnu Esko A1 - Gail Davies A1 - Pers, Tune H A1 - Turley, Patrick A1 - Benyamin, Beben A1 - Chabris, Christopher F A1 - Emilsson, Valur A1 - Andrew D Johnson A1 - Lee, James J A1 - Christiaan de Leeuw A1 - Riccardo E Marioni A1 - Sarah E Medland A1 - Michael B Miller A1 - Rostapshova, Olga A1 - Sven J van der Lee A1 - Anna A E Vinkhuyzen A1 - Amin, Najaf A1 - Dalton C Conley A1 - Derringer, Jaime A1 - Cornelia M van Duijn A1 - Fehrmann, Rudolf A1 - Lude L Franke A1 - Edward L Glaeser A1 - Narelle K Hansell A1 - Caroline Hayward A1 - Iacono, William G A1 - Carla A Ibrahim-Verbaas A1 - Vincent Jaddoe A1 - Karjalainen, Juha A1 - David I Laibson A1 - Paul Lichtenstein A1 - David C Liewald A1 - Patrik K E Magnusson A1 - Nicholas G Martin A1 - McGue, Matt A1 - McMahon, George A1 - Nancy L Pedersen A1 - Pinker, Steven A1 - David J Porteous A1 - Posthuma, Danielle A1 - Fernando Rivadeneira A1 - Smith, Blair H A1 - John M Starr A1 - Henning Tiemeier A1 - Nicholas J Timpson A1 - Trzaskowski, Maciej A1 - André G Uitterlinden A1 - Verhulst, Frank C A1 - Mary E Ward A1 - Margaret J Wright A1 - George Davey Smith A1 - Ian J Deary A1 - Johannesson, Magnus A1 - Plomin, Robert A1 - Peter M Visscher A1 - Daniel J. Benjamin A1 - Cesarini, David A1 - Philipp D Koellinger KW - Cell Adhesion Molecules, Neuronal KW - Cognition KW - Female KW - Humans KW - Learning KW - Male KW - Memory KW - Multifactorial Inheritance KW - Nerve Tissue Proteins KW - Neuronal Plasticity KW - Octamer Transcription Factors KW - Polymorphism, Single Nucleotide KW - Synaptic Transmission AB -

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.

VL - 111 IS - 38 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25201988?dopt=Abstract ER - TY - JOUR T1 - GWAS of 126,559 individuals identifies genetic variants associated with educational attainment. JF - Science Y1 - 2013 A1 - Cornelius A Rietveld A1 - Sarah E Medland A1 - Derringer, Jaime A1 - Yang, Jian A1 - Tõnu Esko A1 - Martin, Nicolas W A1 - Westra, Harm-Jan A1 - Shakhbazov, Konstantin A1 - Abdel Abdellaoui A1 - Agrawal, Arpana A1 - Albrecht, Eva A1 - Alizadeh, Behrooz Z A1 - Amin, Najaf A1 - Barnard, John A1 - Baumeister, Sebastian E A1 - Benke, Kelly S A1 - Bielak, Lawrence F A1 - Boatman, Jeffrey A A1 - Patricia A. Boyle A1 - Gail Davies A1 - Christiaan de Leeuw A1 - Eklund, Niina A1 - Daniel S Evans A1 - Rudolf Ferhmann A1 - Fischer, Krista A1 - Gieger, Christian A1 - Gjessing, Håkon K A1 - Hägg, Sara A1 - Harris, Jennifer R A1 - Caroline Hayward A1 - Holzapfel, Christina A1 - Carla A Ibrahim-Verbaas A1 - Ingelsson, Erik A1 - Jacobsson, Bo A1 - Joshi, Peter K A1 - Jugessur, Astanand A1 - Marika A Kaakinen A1 - Kanoni, Stavroula A1 - Karjalainen, Juha A1 - Kolcic, Ivana A1 - Kristiansson, Kati A1 - Kutalik, Zoltán A1 - J. Lahti A1 - Lee, Sang H A1 - Lin, Peng A1 - Penelope A Lind A1 - Yongmei Liu A1 - Kurt Lohman A1 - Loitfelder, Marisa A1 - McMahon, George A1 - Vidal, Pedro Marques A1 - Osorio Meirelles A1 - Lili Milani A1 - Myhre, Ronny A1 - Nuotio, Marja-Liisa A1 - Christopher J Oldmeadow A1 - Katja E Petrovic A1 - Wouter J Peyrot A1 - Polasek, Ozren A1 - Quaye, Lydia A1 - Reinmaa, Eva A1 - Rice, John P A1 - Rizzi, Thais S A1 - Schmidt, Helena A1 - Schmidt, Reinhold A1 - Albert Vernon Smith A1 - Jennifer A Smith A1 - Toshiko Tanaka A1 - Antonio Terracciano A1 - van der Loos, Matthijs J H M A1 - Vitart, Veronique A1 - Völzke, Henry A1 - Jürgen Wellmann A1 - Lei Yu A1 - Wei Zhao A1 - Allik, Jüri A1 - John R. Attia A1 - Bandinelli, Stefania A1 - Bastardot, François A1 - Jonathan P. Beauchamp A1 - David A Bennett A1 - Klaus Berger A1 - Laura Bierut A1 - Dorret I Boomsma A1 - Bültmann, Ute A1 - Campbell, Harry A1 - Chabris, Christopher F A1 - Cherkas, Lynn A1 - Chung, Mina K A1 - Francesco Cucca A1 - de Andrade, Mariza A1 - Philip L de Jager A1 - De Neve, Jan-Emmanuel A1 - Ian J Deary A1 - George Dedoussis A1 - Deloukas, Panos A1 - Dimitriou, Maria A1 - Guðny Eiríksdóttir A1 - Elderson, Martin F A1 - Johan G Eriksson A1 - Jessica Faul A1 - Luigi Ferrucci A1 - Melissa E Garcia A1 - Grönberg, Henrik A1 - Guðnason, Vilmundur A1 - Hall, Per A1 - Harris, Juliette M A1 - Tamara B Harris A1 - Nicholas D Hastie A1 - Andrew C Heath A1 - Dena G Hernandez A1 - Hoffmann, Wolfgang A1 - Hofman, Adriaan A1 - Holle, Rolf A1 - Holliday, Elizabeth G A1 - Jouke-Jan Hottenga A1 - Iacono, William G A1 - Illig, Thomas A1 - Järvelin, Marjo-Riitta A1 - Kähönen, Mika A1 - Kaprio, Jaakko A1 - Kirkpatrick, Robert M A1 - Kowgier, Matthew A1 - Latvala, Antti A1 - Lenore J Launer A1 - Lawlor, Debbie A A1 - Lehtimäki, Terho A1 - Li, Jingmei A1 - Paul Lichtenstein A1 - Lichtner, Peter A1 - David C Liewald A1 - Pamela A F Madden A1 - Patrik K E Magnusson A1 - Mäkinen, Tomi E A1 - Masala, Marco A1 - McGue, Matt A1 - Andres Metspalu A1 - Mielck, Andreas A1 - Michael B Miller A1 - Grant W Montgomery A1 - Mukherjee, Sutapa A1 - Nyholt, Dale R A1 - Ben A Oostra A1 - Palmer, Lyle J A1 - Aarno Palotie A1 - Brenda W J H Penninx A1 - Markus Perola A1 - Peyser, Patricia A A1 - Preisig, Martin A1 - Katri Räikkönen A1 - Olli T Raitakari A1 - Realo, Anu A1 - Ring, Susan M A1 - Ripatti, Samuli A1 - Fernando Rivadeneira A1 - Rudan, Igor A1 - Rustichini, Aldo A1 - Veikko Salomaa A1 - Sarin, Antti-Pekka A1 - Schlessinger, David A1 - Rodney J Scott A1 - Snieder, Harold A1 - St Pourcain, Beate A1 - John M Starr A1 - Sul, Jae Hoon A1 - Surakka, Ida A1 - Svento, Rauli A1 - Teumer, Alexander A1 - Henning Tiemeier A1 - van Rooij, Frank J A A1 - Van Wagoner, David R A1 - Vartiainen, Erkki A1 - Viikari, Jorma A1 - Vollenweider, Peter A1 - Vonk, Judith M A1 - Waeber, Gérard A1 - David R Weir A1 - Wichmann, H-Erich A1 - Elisabeth Widen A1 - Gonneke Willemsen A1 - James F Wilson A1 - Alan F Wright A1 - Dalton C Conley A1 - Davey-Smith, George A1 - Lude L Franke A1 - Groenen, Patrick J F A1 - Hofman, Albert A1 - Johannesson, Magnus A1 - Sharon L R Kardia A1 - Krueger, Robert F A1 - David I Laibson A1 - Nicholas G Martin A1 - Meyer, Michelle N A1 - Posthuma, Danielle A1 - A. Roy Thurik A1 - Nicholas J Timpson A1 - André G Uitterlinden A1 - Cornelia M van Duijn A1 - Peter M Visscher A1 - Daniel J. Benjamin A1 - Cesarini, David A1 - Philipp D Koellinger KW - Cognition KW - Educational Status KW - Endophenotypes KW - Female KW - Genetic Loci KW - Genome-Wide Association Study KW - Humans KW - Male KW - Multifactorial Inheritance KW - Polymorphism, Single Nucleotide AB -

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.

VL - 340 IS - 6139 U1 - http://www.ncbi.nlm.nih.gov/pubmed/23722424?dopt=Abstract ER -