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1. Mendelian imputation of parental genotypes improves estimates of direct genetic effects

Author

Alexander I. Young, Seyed Moeen Nehzati, Stefania Benonisdottir, Aysu Okbay, Hariharan Jayashankar, Chanwook Lee, David Cesarini, Daniel J. Benjamin, Patrick Turley, Augustine Kong, Economics, Tinbergen Institute, and Amsterdam Neuroscience - Complex Trait Genetics

Subjects
Parents, Genotype, Human Genome, Single Nucleotide, Biological Sciences, Polymorphism, Single Nucleotide, Medical and Health Sciences, Genetics, Humans, 2.1 Biological and endogenous factors, Generic health relevance, Polymorphism, Aetiology, Software, Genome-Wide Association Study, Developmental Biology
Abstract

Effects estimated by genome-wide association studies (GWASs) include effects of alleles in an individual on that individual (direct genetic effects), indirect genetic effects (for example, effects of alleles in parents on offspring through the environment) and bias from confounding. Within-family genetic variation is random, enabling unbiased estimation of direct genetic effects when parents are genotyped. However, parental genotypes are often missing. We introduce a method that imputes missing parental genotypes and estimates direct genetic effects. Our method, implemented in the software package snipar (single-nucleotide imputation of parents), gives more precise estimates of direct genetic effects than existing approaches. Using 39,614 individuals from the UK Biobank with at least one genotyped sibling/parent, we estimate the correlation between direct genetic effects and effects from standard GWASs for nine phenotypes, including educational attainment (r = 0.739, standard error (s.e.) = 0.086) and cognitive ability (r = 0.490, s.e. = 0.086). Our results demonstrate substantial confounding bias in standard GWASs for some phenotypes.

Published
2022

2. Genetic variation associated with differential educational attainment in adults has anticipated associations with school performance in children.

Author

Mary E Ward, George McMahon, Beate St Pourcain, David M Evans, Cornelius A Rietveld, Daniel J Benjamin, Philipp D Koellinger, David Cesarini, Social Science Genetic Association Consortium, George Davey Smith, and Nicholas J Timpson

Subjects
Medicine, Science
Abstract

Genome-wide association study results have yielded evidence for the association of common genetic variants with crude measures of completed educational attainment in adults. Whilst informative, these results do not inform as to the mechanism of these effects or their presence at earlier ages and where educational performance is more routinely and more precisely assessed. Single nucleotide polymorphisms exhibiting genome-wide significant associations with adult educational attainment were combined to derive an unweighted allele score in 5,979 and 6,145 young participants from the Avon Longitudinal Study of Parents and Children with key stage 3 national curriculum test results (SATS results) available at age 13 to 14 years in English and mathematics respectively. Standardised (z-scored) results for English and mathematics showed an expected relationship with sex, with girls exhibiting an advantage over boys in English (0.433 SD (95%CI 0.395, 0.470), p

Published
2014
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3. The molecular genetic architecture of self-employment.

Author

Matthijs J H M van der Loos, Cornelius A Rietveld, Niina Eklund, Philipp D Koellinger, Fernando Rivadeneira, Gonçalo R Abecasis, Georgina A Ankra-Badu, Sebastian E Baumeister, Daniel J Benjamin, Reiner Biffar, Stefan Blankenberg, Dorret I Boomsma, David Cesarini, Francesco Cucca, Eco J C de Geus, George Dedoussis, Panos Deloukas, Maria Dimitriou, Guðny Eiriksdottir, Johan Eriksson, Christian Gieger, Vilmundur Gudnason, Birgit Höhne, Rolf Holle, Jouke-Jan Hottenga, Aaron Isaacs, Marjo-Riitta Järvelin, Magnus Johannesson, Marika Kaakinen, Mika Kähönen, Stavroula Kanoni, Maarit A Laaksonen, Jari Lahti, Lenore J Launer, Terho Lehtimäki, Marisa Loitfelder, Patrik K E Magnusson, Silvia Naitza, Ben A Oostra, Markus Perola, Katja Petrovic, Lydia Quaye, Olli Raitakari, Samuli Ripatti, Paul Scheet, David Schlessinger, Carsten O Schmidt, Helena Schmidt, Reinhold Schmidt, Andrea Senft, Albert V Smith, Timothy D Spector, Ida Surakka, Rauli Svento, Antonio Terracciano, Emmi Tikkanen, Cornelia M van Duijn, Jorma Viikari, Henry Völzke, H-Erich Wichmann, Philipp S Wild, Sara M Willems, Gonneke Willemsen, Frank J A van Rooij, Patrick J F Groenen, André G Uitterlinden, Albert Hofman, and A Roy Thurik

Subjects
Medicine, Science
Abstract

Economic variables such as income, education, and occupation are known to affect mortality and morbidity, such as cardiovascular disease, and have also been shown to be partly heritable. However, very little is known about which genes influence economic variables, although these genes may have both a direct and an indirect effect on health. We report results from the first large-scale collaboration that studies the molecular genetic architecture of an economic variable-entrepreneurship-that was operationalized using self-employment, a widely-available proxy. Our results suggest that common SNPs when considered jointly explain about half of the narrow-sense heritability of self-employment estimated in twin data (σ(g)(2)/σ(P)(2) = 25%, h(2) = 55%). However, a meta-analysis of genome-wide association studies across sixteen studies comprising 50,627 participants did not identify genome-wide significant SNPs. 58 SNPs with p

Published
2013
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4. Genomic analysis of diet composition finds novel loci and associations with health and lifestyle

Author

Fumiaki Imamura, George Davey Smith, Chanwook Lee, Nicholas J. Wareham, M. Arfan Ikram, George McMahon, Aysu Okbay, Frank J. A. van Rooij, Peter Bowers, Carson C. Chow, Patrick Turley, Ronald de Vlaming, Jian'an Luan, Oscar H. Franco, Trudy Voortman, Daniel J. Benjamin, André G. Uitterlinden, Casper A.P. Burik, Nita G. Forouhi, K. Paige Harden, Pauline M Emmett, Cornelius A. Rietveld, Juan R. González, Bruce H. R. Wolffenbuttel, Philipp Koellinger, Mark Alan Fontana, James J. Lee, David Cesarini, Harold Snieder, Kim Valeska Emilie Braun, Emma L Anderson, Jana V. van Vliet-Ostaptchouk, Peter J. van der Most, Richard Karlsson Linnér, Susan M. Ring, Claudia Langenberg, Tonũ Esko, Fernando Rivadeneira, Kaitlin H Wade, Jessica C. Kiefte-de Jong, Taulant Muka, Mohsen Ghanbari, S. Fleur W. Meddens, Linnér, Richard Karlsson [0000-0001-7839-2858], Okbay, Aysu [0000-0002-5170-7781], Rietveld, Cornelius A [0000-0003-4053-1861], Ghanbari, Mohsen [0000-0002-9476-7143], Imamura, Fumiaki [0000-0002-6841-8396], van der Most, Peter J [0000-0001-8450-3518], Voortman, Trudy [0000-0003-2830-6813], Wade, Kaitlin H [0000-0003-3362-6280], Braun, Kim VE [0000-0001-8738-4139], Gonzalez, Juan R [0000-0003-3267-2146], Kiefte-de Jong, Jessica C [0000-0002-8136-0918], Langenberg, Claudia [0000-0002-5017-7344], Luan, Jian'an [0000-0003-3137-6337], Ring, Susan [0000-0003-3103-9330], Rivadeneira, Fernando [0000-0001-9435-9441], Snieder, Harold [0000-0003-1949-2298], van Rooij, Frank JA [0000-0002-8600-9852], Smith, George Davey [0000-0002-1407-8314], Forouhi, Nita G [0000-0002-5041-248X], Ikram, M Arfan [0000-0003-0372-8585], Uitterlinden, Andre G [0000-0002-7276-3387], van Vliet-Ostaptchouk, Jana V [0000-0002-7943-3153], Lee, James J [0000-0001-6547-5128], Benjamin, Daniel J [0000-0002-2642-5416], Apollo - University of Cambridge Repository, Rietveld, Cornelius A. [0000-0003-4053-1861], van der Most, Peter J. [0000-0001-8450-3518], Wade, Kaitlin H. [0000-0003-3362-6280], Braun, Kim V. E. [0000-0001-8738-4139], Gonzalez, Juan R. [0000-0003-3267-2146], Kiefte-de Jong, Jessica C. [0000-0002-8136-0918], Luan, Jian’an [0000-0003-3137-6337], van Rooij, Frank J. A. [0000-0002-8600-9852], Forouhi, Nita G. [0000-0002-5041-248X], Ikram, M. Arfan [0000-0003-0372-8585], Uitterlinden, Andre G. [0000-0002-7276-3387], van Vliet-Ostaptchouk, Jana V. [0000-0002-7943-3153], Lee, James J. [0000-0001-6547-5128], Benjamin, Daniel J. [0000-0002-2642-5416], Applied Economics, Life Course Epidemiology (LCE), Lifestyle Medicine (LM), Center for Liver, Digestive and Metabolic Diseases (CLDM), Economics, and Amsterdam Neuroscience - Complex Trait Genetics

Subjects
0301 basic medicine, BETA-KLOTHO, PROTEIN-INTAKE, LD SCORE REGRESSION, Diseases, Genome-wide association study, Type 2 diabetes, METABOLIC-ACTIVITY, OBESITY RISK, Cardiovascular, Medical and Health Sciences, CHAIN AMINO-ACIDS, Body Mass Index, 631/208, 0302 clinical medicine, 2.1 Biological and endogenous factors, WIDE ASSOCIATION, SOCIOECONOMIC-STATUS, 030212 general & internal medicine, Aetiology, Psychiatry, 2. Zero hunger, Genetics, 692/699, Diabetes, article, Genomics, Biological Sciences, SDG 11 - Sustainable Cities and Communities, 3. Good health, Psychiatry and Mental health, SDG 1 - No Poverty, Type 2, WEIGHT-LOSS, Single-nucleotide polymorphism, Biology, 23andMe Research Team, Genetic correlation, 03 medical and health sciences, Cellular and Molecular Neuroscience, Lifelines Cohort Study, Behavioral and Social Science, Diabetes Mellitus, medicine, Humans, Obesity, Molecular Biology, Life Style, Metabolic and endocrine, Nutrition, Genetic association, EPIC- InterAct Consortium, Prevention, Human Genome, Psychology and Cognitive Sciences, medicine.disease, Genetic architecture, Diet, BODY-MASS INDEX, 030104 developmental biology, Diabetes Mellitus, Type 2, Body mass index, Genome-Wide Association Study
Abstract

We conducted genome-wide association studies (GWAS) of relative intake from the macronutrients fat, protein, carbohydrates, and sugar in over 235,000 individuals of European ancestries. We identified 21 unique, approximately independent lead SNPs. Fourteen lead SNPs are uniquely associated with one macronutrient at genome-wide significance (P < 5 × 10-8), while five of the 21 lead SNPs reach suggestive significance (P < 1 × 10-5) for at least one other macronutrient. While the phenotypes are genetically correlated, each phenotype carries a partially unique genetic architecture. Relative protein intake exhibits the strongest relationships with poor health, including positive genetic associations with obesity, type 2 diabetes, and heart disease (rg ≈ 0.15-0.5). In contrast, relative carbohydrate and sugar intake have negative genetic correlations with waist circumference, waist-hip ratio, and neighborhood deprivation (|rg| ≈ 0.1-0.3) and positive genetic correlations with physical activity (rg ≈ 0.1 and 0.2). Relative fat intake has no consistent pattern of genetic correlations with poor health but has a negative genetic correlation with educational attainment (rg ≈-0.1). Although our analyses do not allow us to draw causal conclusions, we find no evidence of negative health consequences associated with relative carbohydrate, sugar, or fat intake. However, our results are consistent with the hypothesis that relative protein intake plays a role in the etiology of metabolic dysfunction. This research was carried out under the auspices of the Social Science Genetic Association Consortium (SSGAC, https://www.thessgac.org/). The research has also been conducted using the UK Biobank Resource under Application Number 11425. The study was supported by funding from the Ragnar Söderberg Foundation (E9/11 and E42/15), the Swedish Research Council (421-2013-1061), The Jan Wallander and Tom Hedelius Foundation, an ERC Consolidator Grant to Philipp Koellinger (647648 EdGe), the Pershing Square Fund of the Foundations of Human Behavior, The Open Philanthropy Project (2016-152872, 010623-00001), and the NIA/NIH through grants P01-AG005842, P01-AG005842-20S2, P30-AG012810, and T32-AG000186-23 to NBER, and R01-AG042568-02 and R56-AG042568-04 to the University of Southern California. CCC was supported by the Intramural Research Program of the NIH/NIDDK and thanks Kevin Hall for informative discussions. PME was funded by Nestlé Nutrition. We thank the DietGen and CHARGE consortia for sharing diet-composition GWAS summary statistics, and we thank 23andMe, Inc., for sharing physical activity GWAS summary statistics. A full list of acknowledgements is provided in Supplementary Information 13.

Published
2020

5. Self-reported wellbeing indicators are a valuable complement to traditional economic indicators but are not yet ready to compete with them

Author

Daniel J. Benjamin, Miles S. Kimball, Kristen B. Cooper, and Ori Heffetz

Subjects
Index (economics), Public economics, 05 social sciences, Pharmaceutical Science, Article, Complementary and alternative medicine, Economic indicator, Order (exchange), 0502 economics and business, Pharmacology (medical), 050207 economics, Psychology, 050205 econometrics, Complement (set theory)
Abstract

We join the call for governments to routinely collect survey-based measures of self-reported wellbeing and for researchers to study them. We list a number of challenges that have to be overcome in order for these measures to eventually achieve a status that is competitive with traditional economic indicators. We discuss in more detail one of the challenges, comprehensiveness: single-question wellbeing measures do not seem to fully capture what people care about. We briefly review the existing evidence, suggesting that survey respondents, when asked to make real or hypothetical trade-offs, would not always choose to maximize their predicted response to single-question wellbeing measures. The deviations appear systematic, and they persist under conditions where alternative explanations are less plausible. We also review an approach for combining single-question measures into a more comprehensive wellbeing index – an approach that itself is not free of ongoing theoretical and implementational challenges, but that we view as a promising direction.

Published
2020

6. A consensus-based transparency checklist

Author

Brendan Nyhan, Jarret T. Crawford, Christopher D. Chambers, Wiebke Bleidorn, Daniel J. Benjamin, Alice S. Carter, Joseph Cesario, Fiammetta Cosci, Dolores Albarracín, Eric Johnson, Morton Ann Gernsbacher, Marcus R. Munafò, Agneta Fisher, Debra Lieberman, Simine Vazire, Donald P. Green, Jeffrey M. Pollack, George C. Banks, Šimon Kucharský, Derek M. Isaacowitz, Mike Cortese, Alexandra Sarafoglou, Lisa L. Harlow, Randall W. Engle, Fernando Hoces de la Guardia, Ronan M. Conroy, Alexandra M. Freund, Mark Fichman, Janet Kolodner, Daniel J. Simons, Nicole D. Anderson, Kai J. Jonas, Nelson Cowan, Charles Clifton, Zoltan Kekecs, Eveline A. Crone, Robert L. Greene, John Antonakis, Candice C. Morey, D. Stephen Lindsay, Lea Moersdorf, Scott O. Lilienfeld, Balazs Aczel, Gordon D. Logan, Stavroula Kousta, Simon Farrell, Eric-Jan Wagenmakers, Jelte M. Wicherts, John J. Curtin, John P. A. Ioannidis, David R. Shanks, Mitja D. Back, Pasco Fearon, Cristina Cacciari, Christopher J. Sullivan, Wendy Berry Mendes, Benjamin R. Newell, Christopher G. Beevers, Andrew A. Bennett, M. Gareth Gaskell, Roger Giner-Sorolla, Willem E. Frankenhuis, Andrew Gelman, Ty W. Boyer, Hal R. Arkes, Barnabas Szaszi, Harold Pashler, Psychologische Methodenleer (Psychologie, FMG), Psychology Other Research (FMG), Department of Methodology and Statistics, Section Applied Social Psychology, and RS: FPN WSP II

Subjects
Scientific community, Consensus, Social Psychology, Delphi Technique, Computer science, Information Dissemination, Delphi method, MEDLINE, Social Sciences, Experimental and Cognitive Psychology, Guidelines as Topic, Social Development, Behavioral Research/standards, Social sciences, World Wide Web, 03 medical and health sciences, Behavioral Neuroscience, 0302 clinical medicine, Behavioral Research, Humans, Periodicals as Topic, Checklist, Author Correction, 030304 developmental biology, 0303 health sciences, Comment, Transparency (behavior), Public repository, Social Sciences/standards, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, 030217 neurology & neurosurgery
Abstract

Contains fulltext : 214941.pdf (Publisher’s version ) (Open Access) We present a consensus-based checklist to improve and document the transparency of research reports in social and behavioural research. An accompanying online application allows users to complete the form and generate a report that they can submit with their manuscript or post to a public repository. 3 p.

Published
2020

7. Author correction: A consensus-based transparency checklist

Author

Pasco Fearon, Robert L. Greene, Marcus R. Munafò, Cristina Cacciari, Christopher J. Sullivan, Kai J. Jonas, Daniel J. Benjamin, Simine Vazire, Mark Fichman, Eric-Jan Wagenmakers, Dolores Albarracín, Morton Ann Gernsbacher, Brendan Nyhan, Mitja D. Back, Jeffrey M. Pollack, Mike Cortese, Benjamin R. Newell, D. Stephen Lindsay, Christopher G. Beevers, M. Gareth Gaskell, Šimon Kucharský, Randall W. Engle, Harold Pashler, Roger Giner-Sorolla, Lea Moersdorf, Alice S. Carter, Debra Lieberman, Joseph Cesario, Fiammetta Cosci, Eric Johnson, Jelte M. Wicherts, Wendy Berry Mendes, Charles Clifton, John J. Curtin, John P. A. Ioannidis, Scott O. Lilienfeld, Andrew A. Bennett, George C. Banks, Jarret T. Crawford, Andrew Gelman, Simon Farrell, Hal R. Arkes, Daniel J. Simons, Christopher D. Chambers, Alexandra M. Freund, Willem E. Frankenhuis, Ty W. Boyer, Janet Kolodner, Agneta Fisher, David R. Shanks, Barnabas Szaszi, Fernando Hoces de la Guardia, Balazs Aczel, Zoltan Kekecs, John Antonakis, Donald P. Green, Nelson Cowan, Eveline A. Crone, Lisa L. Harlow, Nicole D. Anderson, Wiebke Bleidorn, Gordon D. Logan, Stavroula Kousta, Derek M. Isaacowitz, Ronan M. Conroy, Candice C. Morey, and Alexandra Sarafoglou

Subjects
Behavioral Neuroscience, Social Psychology, media_common.quotation_subject, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Experimental and Cognitive Psychology, Art, Social Development, Humanities, media_common
Abstract

Author(s): Aczel, Balazs; Szaszi, Barnabas; Sarafoglou, Alexandra; Kekecs, Zoltan; Kucharský, Simon; Benjamin, Daniel; Chambers, Christopher D; Fisher, Agneta; Gelman, Andrew; Gernsbacher, Morton A; Ioannidis, John P; Johnson, Eric; Jonas, Kai; Kousta, Stavroula; Lilienfeld, Scott O; Lindsay, D Stephen; Morey, Candice C; Munafo, Marcus; Newell, Benjamin R; Pashler, Harold; Shanks, David R; Simons, Daniel J; Wicherts, Jelte M; Albarracin, Dolores; Anderson, Nicole D; Antonakis, John; Arkes, Hal R; Back, Mitja D; Banks, George C; Beevers, Christopher; Bennett, Andrew A; Bleidorn, Wiebke; Boyer, Ty W; Cacciari, Cristina; Carter, Alice S; Cesario, Joseph; Clifton, Charles; Conroy, Ronan M; Cortese, Mike; Cosci, Fiammetta; Cowan, Nelson; Crawford, Jarret; Crone, Eveline A; Curtin, John; Engle, Randall; Farrell, Simon; Fearon, Pasco; Fichman, Mark; Frankenhuis, Willem; Freund, Alexandra M; Gaskell, M Gareth; Giner-Sorolla, Roger; Green, Don P; Greene, Robert L; Harlow, Lisa L; de la Guardia, Fernando Hoces; Isaacowitz, Derek; Kolodner, Janet; Lieberman, Debra; Logan, Gordon D; Mendes, Wendy B; Moersdorf, Lea; Nyhan, Brendan; Pollack, Jeffrey; Sullivan, Christopher; Vazire, Simine; Wagenmakers, Eric-Jan | Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2020

8. Resource profile and user guide of the Polygenic Index Repository

Author

Hariharan Jayashankar, David Laibson, Nancy Wang, William G. Iacono, Avshalom Caspi, Karen Sugden, Patrik K. E. Magnusson, Tõnu Esko, Kathleen Mullan Harris, Alexander I. Young, Travis T. Mallard, Terrie E. Moffitt, Patrick Turley, Jeremy Freese, Grant Goldman, Richard Karlsson Linnér, Pamela Herd, Michael Bennett, Benjamin Williams, Sven Oskarsson, Rafael Ahlskog, Aaron Kleinman, Peter M. Visscher, Elliot M. Tucker-Drob, David Cesarini, Aysu Okbay, Magnus Johannesson, Olesya Ajnakina, Philipp Koellinger, Joel Becker, Matt McGue, Michelle N. Meyer, Casper A.P. Burik, Jonathan P. Beauchamp, Richie Poulton, K. Paige Harden, Lili Milani, Daniel W. Belsky, David A. Hinds, Daniel J. Benjamin, David L. Corcoran, Andrew Steptoe, Economics, Amsterdam Neuroscience - Complex Trait Genetics, and Tinbergen Institute

Subjects
Data Analysis, Multifactorial Inheritance, Social Psychology, Computer science, Experimental and Cognitive Psychology, Latent variable, computer.software_genre, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, Behavioral Neuroscience, 0302 clinical medicine, Resource (project management), Databases, Genetic, Humans, Proxy (statistics), 030304 developmental biology, computer.programming_language, 0303 health sciences, Estimator, Python (programming language), Biobank, Key (cryptography), Data mining, Construct (philosophy), computer, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

Polygenic indexes (PGIs) are DNA-based predictors. Their value for research in many scientific disciplines is rapidly growing. As a resource for researchers, we used a consistent methodology to construct PGIs for 47 phenotypes in 11 datasets. To maximize the PGIs’ prediction accuracies, we constructed them using genome-wide association studies—some not previously published—from multiple data sources, including 23andMe and UK Biobank. We present a theoretical framework to help interpret analyses involving PGIs. A key insight is that a PGI can be understood as an unbiased but noisy measure of a latent variable we call the “additive SNP factor.” Regressions in which the true regressor is the additive SNP factor but the PGI is used as its proxy therefore suffer from errors-in-variables bias. We derive an estimator that corrects for the bias, illustrate the correction, and make a Python tool for implementing it publicly available.

Published
2021

9. Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences1

Author

Edward Kong, Pascal Timshel, Danielle Posthuma, Tõnu Esko, Maël Lebreton, Kathleen Mullan Harris, Philipp Koellinger, Murray B. Stein, Abraham A. Palmer, Urs Fischbacher, Robert J. Ursano, Erdogan Taskesen, Peter Eibich, Paul R. H. J. Timmers, Anke R. Hammerschlag, Ann H. Caplin, Jian Yang, Sandra Sanchez-Roige, Peter K. Joshi, Matthias Sutter, Pierre Fontanillas, Chia-Yen Chen, Albert Hofman, Patrick Turley, David A. Hinds, Futao Zhang, David Cesarini, Christina M. Lill, Laura Buzdugan, Ville Karhunen, Abdel Abdellaoui, S. Fleur W. Meddens, Henning Tiemeier, Christian L. Zund, Gert G. Wagner, Richard Karlsson Linnér, Lars Bertram, David W. Clark, Roy Thurik, André G. Uitterlinden, Maciej Trzaskowski, Mohammad Arfan Ikram, David Laibson, Cornelius A. Rietveld, Arcadi Navarro, Ernst Fehr, Yang Wu, Matthew B. McQueen, Ronald C. Kessler, Magnus Johannesson, Patrick J. F. Groenen, Gregor Hasler, James F. Wilson, Daniel Schunk, Stephen P. Tino, Pietro Biroli, Mark Alan Fontana, Juan R. González, Meena Kumari, Gerardus A. Meddens, Jonathan P. Beauchamp, Michelle N. Meyer, Jason D. Boardman, James J. Lee, Carlos Morcillo-Suarez, Aaron Kleinman, Minna Männikkö, Andrew Conlin, Adam Auton, Tune H. Pers, Michel G. Nivard, Ronald de Vlaming, Jon White, Robert Karlsson, Daniel J. Benjamin, Maarten Kooyman, Jacob Gratten, Aysu Okbay, Remy Z. Levin, Melissa C. Smart, Harriet de Wit, Conor C. Dolan, Frank J. A. van Rooij, Patrik K. E. Magnusson, Sonia Jain, Rauli Svento, Klaus M. Schmidt, Dorret I. Boomsma, Gerard Muntané, James MacKillop, Robbee Wedow, and Yanchun Bao

Subjects
Genetics, 0303 health sciences, Gabaergic neurotransmission, Single-nucleotide polymorphism, Genome-wide association study, Biology, Phenotype, 03 medical and health sciences, 0302 clinical medicine, SNP, Gene, 030217 neurology & neurosurgery, 030304 developmental biology, Genetic association
Abstract

Humans vary substantially in their willingness to take risks. In a combined sample of over one million individuals, we conducted genome-wide association studies (GWAS) of general risk tolerance, adventurousness, and risky behaviors in the driving, drinking, smoking, and sexual domains. We identified 611 approximately independent genetic loci associated with at least one of our phenotypes, including 124 with general risk tolerance. We report evidence of substantial shared genetic influences across general risk tolerance and risky behaviors: 72 of the 124 general risk tolerance loci contain a lead SNP for at least one of our other GWAS, and general risk tolerance is moderately to strongly genetically correlated (to 0.50) with a range of risky behaviors. Bioinformatics analyses imply that genes near general-risk-tolerance-associated SNPs are highly expressed in brain tissues and point to a role for glutamatergic and GABAergic neurotransmission. We find no evidence of enrichment for genes previously hypothesized to relate to risk tolerance.

Published
2018
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10. An epigenome-wide association study of educational attainment (n = 10,767)

Author

George Davey Smith, Sara Hägg, Antti Latvala, Khadeeja Ismail, Cisca Wijmenga, Karen A. Mather, Laura Baglietto, Miina Ollikainen, Allison M. Hodge, Jari Lahti, Ian J. Deary, Andrew J Simpkin, Nicholas G. Martin, Ilkka Seppälä, Annette Peters, Silva Kasela, Riccardo E. Marioni, Mikko Hurme, Lisette Stolk, Pooja R. Mandaviya, Tõnu Esko, Kirsi Auro, Gianluca Severi, Jadwiga Buchwald, Silvia Polidoro, Yunzhang Wang, Neil M Davies, Pauliina Karell, Danielle Posthuma, Paolo Vineis, Roger L. Milne, Clemens Baumbach, Magnus Johannesson, Erdogan Taskesen, Richard Karlsson Linnér, Steve Horvath, Jaakko Kaprio, André G. Uitterlinden, Kyoko Watanabe, Christian Gieger, John M. Starr, Anni Joensuu, Melanie Waldenberger, Alison Pattie, Cornelius A. Rietveld, Pekka Jousilahti, Nicola J. Armstrong, Giovanni Fiorito, Sarah E. Medland, Lude Franke, Joyce B. C van Meurs, Graham G. Giles, Mika Kähönen, Andres Metspalu, Marc Jan Bonder, Lili Milani, Margaret J. Wright, Caroline L Relton, Terho Lehtimäki, Philipp Koellinger, Nancy L. Pedersen, Markus Perola, Elisabeth B. Binder, Allan F. McRae, Stella Iurato, Katri Räikkönen, Daniel J. Benjamin, Sarah E. Harris, Johan G. Eriksson, Perminder S. Sachdev, and Olli T. Raitakari

Subjects
Genetics, 0303 health sciences, Epigenome, Biology, Bioinformatics, Educational attainment, 03 medical and health sciences, 0302 clinical medicine, CpG site, DNA methylation, 030212 general & internal medicine, Epigenetics, Association (psychology), Body mass index, 030304 developmental biology, Cohort study
Abstract

The epigenome has been shown to be influenced by biological factors, such as disease status, and environmental factors, such as smoking, alcohol consumption, and body mass index. Although there is a widespread perception that environmental influences on the epigenome are pervasive and profound, there has been little evidence to date in humans with respect to environmental factors that are biologically distal. Here, we provide evidence on the associations between epigenetic modifications—in our case, CpG methylation—and educational attainment (EA), a biologically distal environmental factor that is arguably among of the most important life-shaping experiences for individuals. Specifically, we report the results of an epigenome-wide association study meta-analysis of EA based on data from 27 cohort studies with a total of 10,767 individuals. While we find that 9 CpG probes are significantly associated with EA, only two remain associated when we restrict the sample to never-smokers. These two are known to be strongly associated with maternal smoking during pregnancy, and thus their association with EA could be due to correlation between EA and maternal smoking. Moreover, their effect sizes on EA are far smaller than the known associations between CpG probes and biologically proximal environmental factors. Two analyses that combine the effects of many probes—polygenic methylation score and epigenetic-clock analyses—both suggest small associations with EA. If our findings regarding EA can be generalized to other biologically distal environmental factors, then they cast doubt on the hypothesis that such factors have large effects on the epigenome.

Published
2017
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11. Author Correction: Multi-trait analysis of genome-wide association summary statistics using MTAG

Author

Omeed Maghzian, David Laibson, Magnus Johannesson, Daniel J. Benjamin, James J. Lee, Mark Alan Fontana, Meghan Zacher, Aysu Okbay, Patrik K. E. Magnusson, Tuan Anh Nguyen-Viet, David Cesarini, Peter M. Visscher, Patrick Turley, Robbee Wedow, Sven Oskarsson, Nicholas A. Furlotte, Raymond K. Walters, Benjamin M. Neale, Economics, and Amsterdam Neuroscience - Complex Trait Genetics

Subjects
Competing interests, Statement (logic), Published Erratum, Multi trait, Genetics, MEDLINE, Genome-wide association study, Genomics, Biology, Summary statistics, Data science
Abstract

In the version of the paper initially published, no competing interests were declared. The ‘Competing interests’ statement should have stated that B.M.N. is on the Scientific Advisory Board of Deep Genomics. The error has been corrected in the HTML and PDF versions of the article.

Published
2019

12. Molecular genetics and subjective well-being

Author

Nancy L. Pedersen, Magnus Johannesson, Cornelius A. Rietveld, Henning Tiemeier, Daniel J. Benjamin, Philipp Koellinger, Patrik K. E. Magnusson, Jan-Emmanuel De Neve, Robert F. Krueger, Meike Bartels, David Cesarini, Erasmus School of Economics, Applied Economics, Child and Adolescent Psychiatry / Psychology, Ophthalmology, EMGO+ - Mental Health, Tinbergen Institute, Amsterdam Neuroscience - Complex Trait Genetics, Biological Psychology, and ABS Other Research (FEB)

Subjects
Male, H Social Sciences (General), Genotype, BF Psychology, media_common.quotation_subject, Population, jel:D60, Happiness, Social Sciences, Genome-wide association study, Personal Satisfaction, QH426 Genetics, Polymorphism, Single Nucleotide, jel:D03, 03 medical and health sciences, 0302 clinical medicine, Optimism, Gene Frequency, Political science, Surveys and Questionnaires, Twins, Dizygotic, Personality, Humans, Registries, Social science, Subjective well-being, education, 030304 developmental biology, media_common, Aged, Netherlands, Aged, 80 and over, Sweden, 0303 health sciences, education.field_of_study, Multidisciplinary, Q Science (General), Variance (accounting), Twins, Monozygotic, Heritability, Middle Aged, subjective well-being, heritability, genetics, GREML, Female, 030217 neurology & neurosurgery, Demography
Abstract

Subjective well-being (SWB) is a major topic of research across the social sciences. Twin and family studies have found that genetic factors may account for as much as 30–40% of the variance in SWB. Here, we study genetic contributions to SWB in a pooled sample of ≈11,500 unrelated, comprehensively-genotyped Swedish and Dutch individuals. We apply a recently developed method to estimate “common narrow heritability”: the fraction of variance in SWB that can be explained by the cumulative additive effects of genetic polymorphisms that are common in the population. Our estimates are 5–10% for single-question survey measures of SWB, and 12–18% after correction for measurement error in the SWB measures. Our results suggest guarded optimism about the prospects of using genetic data in SWB research because, although the common narrow heritability is not large, the polymorphisms that contribute to it could feasibly be discovered with a sufficiently large sample of individuals.

Published
2013

13. Distinct loci in the CHRNA5/CHRNA3/CHRNB4 gene cluster are associated with onset of regular smoking

Author

Nadia N. Hansel, Shizhong Han, Gary E. Swan, Bao-Zhu Yang, Jonathan Marchini, Daniel J. Benjamin, Helena Furberg, Sanjay Shete, Yu-Ching Cheng, Alistair S. Hall, Christian J. Hopfer, Brenda W.J.H. Penninx, Nilesh J. Samani, Tellervo Korhonen, Maria Teresa Landi, David J Couper, Hyman Hops, Stephen Kittner, Jouke-Jan Hottenga, Markus M. Nöthen, Susan E. Short, Neil E. Caporaso, Braxton D. Mitchell, Richard A. Grucza, Ingo Ruczinski, Jorma Viikari, Leo-Pekka Lyytikäinen, Mary L. Marazita, Steven M. Levy, Annette M. Hartmann, Pekka Jousilahti, Bettina Konte, Kenneth S. Kendler, Kauko Heikkilä, Hans J. Grabe, Dorret I. Boomsma, Henry Völzke, Terri H. Beaty, Mark Leppert, Tiina Laatikainen, Robin C. Corley, Martha Michel, Naomi Breslau, Jenni Hällfors, Magnus Johannesson, Matthias Nauck, Philipp Koellinger, Laura J. Bierut, John K. Hewitt, Margaret R. Spitz, Eric Boerwinkle, Nicholas G. Martin, Dorothy K. Hatsukami, Francesco Cucca, Ulla Broms, Anthony J. Balmforth, Marcella Rietschel, Nora Franceschini, Penelope A. Lind, Victoria L. Stevens, Robert B. Weiss, Qingyi Wei, Olli T. Raitakari, Hilary Coon, Angela S. Wenzlaff, Marika Kaakinen, Nathan A. Gillespie, Steven H. Aggen, John R. Shaffer, John R. Thompson, Alexander Teumer, Juzhong Sun, Danielle M. Dick, Jason Z. Liu, Mika Kähönen, Nicole Vogelzangs, Ian B. Hickie, Andrew W. Bergen, Veikko Salomaa, Tatiana Foroud, Francesca Ducci, Dan Rujescu, Fangyi Gu, Ina Giegling, Grant W. Montgomery, Patrik K. E. Magnusson, Daniel W. McNeil, Sven Cichon, Sarah M. Hartz, Nicole R. Hoft, Dale S. Cannon, Ann G. Schwartz, Chenhui Jiang, Peter D. Paré, Xiangning Chen, Sebastian E. Baumeister, Joel Gelernter, Nilanjan Chatterjee, Kathleen C. Barnes, William Wheeler, Terho Lehtimäki, Jingchun Chen, Michele L. Pergadia, Kari E. North, Howard J. Edenberg, Gonneke Willemsen, Jaakko Kaprio, Jacqueline M. Vink, Sarah H. Stephens, Clyde Francks, Andrew C. Heath, Josef Frank, Christopher I. Amos, Nancy L. Saccone, Pamela A. F. Madden, Marjo-Riitta Järvelin, Rasika A. Mathias, Marissa A. Ehringer, Tanda Murray, David Cesarini, Eric O. Johnson, Younghun Han, Peter Kraft, Juha Veijola, Nicole Dueker, Sarah E. Medland, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Mental Health, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, Biological Psychology, Tinbergen Institute, Amsterdam Neuroscience - Complex Trait Genetics, ABS Other Research (FEB), Psychiatry, NCA - Brain mechanisms in health and disease, NCA - Neurobiology of mental health, and EMGO - Mental health

Subjects
Male, Oncology, Netherlands Twin Register (NTR), Linkage disequilibrium, Internationality, Epidemiology, Receptors, Nicotinic, Linkage Disequilibrium, Nicotine, chemistry.chemical_compound, 0302 clinical medicine, Age of Onset, Cotinine, Genetics (clinical), Genetics, 0303 health sciences, CHRNA5, Smoking, Tobacco Use Disorder, 3. Good health, Phenotype, Multigene Family, Female, medicine.drug, medicine.medical_specialty, Adolescent, Nerve Tissue Proteins, Single-nucleotide polymorphism, Quantitative trait locus, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, Lung cancer, 030304 developmental biology, ta3121, medicine.disease, chemistry, Genetic Loci, biology.protein, Age of onset, 030217 neurology & neurosurgery
Abstract

Neuronal nicotinic acetylcholine receptor (nAChR) genes (CHRNA5/CHRNA3/CHRNB4) have been reproducibly associated with nicotine dependence, smoking behaviors, and lung cancer risk. Of the few reports that have focused on early smoking behaviors, association results have been mixed. This meta-analysis examines early smoking phenotypes and SNPs in the gene cluster to determine: (1) whether the most robust association signal in this region (rs16969968) for other smoking behaviors is also associated with early behaviors, and/or (2) if additional statistically independent signals are important in early smoking. We focused on two phenotypes: age of tobacco initiation (AOI) and age of first regular tobacco use (AOS). This study included 56,034 subjects (41 groups) spanning nine countries and evaluated five SNPs including rs1948, rs16969968, rs578776, rs588765, and rs684513. Each dataset was analyzed using a centrally generated script. Meta-analyses were conducted from summary statistics. AOS yielded significant associations with SNPs rs578776 (beta = 0.02, P = 0.004), rs1948 (beta = 0.023, P = 0.018), and rs684513 (beta = 0.032, P = 0.017), indicating protective effects. There were no significant associations for the AOI phenotype. Importantly, rs16969968, the most replicated signal in this region for nicotine dependence, cigarettes per day, and cotinine levels, was not associated with AOI (P = 0.59) or AOS (P = 0.92). These results provide important insight into the complexity of smoking behavior phenotypes, and suggest that association signals in the CHRNA5/A3/B4 gene cluster affecting early smoking behaviors may be different from those affecting the mature nicotine dependence phenotype. © 2013 WILEY PERIODICALS, INC.

Published
2016

14. Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses

Author

Sharon L.R. Kardia, Melinda Mills, Ian J. Deary, Sven Bergmann, Magnus Johannesson, Igor Rudan, Nicholas J. Timpson, Richa Gupta, Hester M. den Ruijter, Rico Rueedi, Lars Bertram, Juliette Harris, Jennifer A. Smith, Eero Kajantie, Jian Yang, David C. Liewald, Ronald de Vlaming, Anu Realo, Jessica D. Faul, Patrik K. E. Magnusson, Jadwiga Buchwald, Philip L. De Jager, Rajesh Rawal, Marisa Koini, K. Petrovic, Unnur Thorsteinsdottir, Pedro Marques-Vidal, Roy Thurik, Evie Stergiakouli, Ivana Kolcic, William G. Iacono, Laura D. Kubzansky, Jaakko Kaprio, Behrooz Z. Alizadeh, Samantha Cherney, Reinhold Schmidt, Vilmundur Gudnason, Nicholas A. Furlotte, Nicholas G. Martin, Delilah Zabaneh, Rebecca T. Emeny, Eco J. C. de Geus, Klaus Berger, Lude Franke, Sven J. van der Lee, S. Fleur W. Meddens, Bart M. L. Baselmans, Dalton Conley, Jouke-Jan Hottenga, David A. Bennett, Saskia Haitjema, Jun Ding, Elina Hyppönen, Kari Stefansson, Henning Tiemeier, Grant W. Montgomery, Michelle N. Meyer, James J. Lee, Aysu Okbay, Lei Yu, Gyda Bjornsdottir, Marie Henrike Geisel, Albertine J. Oldehinkel, Liisa Keltikangas-Järvinen, George Davey Smith, Harold Snieder, Juho Wedenoja, Frits R. Rosendaal, Michel G. Nivard, Simon R. Cox, Christine Power, Dorret I. Boomsma, Börge Schmidt, David A. Hinds, Philipp Koellinger, Harm-Jan Westra, Terho Lehtimäki, Alison Pattie, Jan-Emmanuel De Neve, Torben Hansen, John M. Starr, Albert V. Smith, Antonio Terracciano, Juergen Wellmann, Albert Hofman, Katri Räikkönen, Patrick Turley, Andrew Steptoe, Jimmy Z. Liu, Evelin Mihailov, Jari Lahti, Marika Kaakinen, David R. Weir, Cornelia M. van Duijn, Maciej Trzaskowski, David Cesarini, Najaf Amin, Lydia Quaye, Sara M. Willems, Ghazaleh Fatemifar, Christopher Oldmeadow, Ville Karhunen, Alana Cavadino, Juan R. González, Caroline Hayward, Penelope A. Lind, Tamara B. Harris, Jaime Derringer, Camelia C. Minică, Jacob Gratten, Patrick J. F. Groenen, Ozren Polasek, Anu Loukola, Peter Vollenweider, Christian Gieger, Rodney J. Scott, Lindsay K. Matteson, Meike Bartels, Andrew Bakshi, David Laibson, Andrew C. Heath, Daniel J. Benjamin, Stephen S. Rich, Claire M. A. Haworth, C.A. Hartman, Angelina R. Sutin, Tian Liu, Johan G. Eriksson, Robert Plomin, Francesco Cucca, John Attia, Tarunveer S. Ahluwalia, Andreas J. Forstner, Gudmar Thorleifsson, Rauli Svento, Ute Bültmann, Olli T. Raitakari, Karl-Heinz Jöckel, Mark Alan Fontana, Oliver S. P. Davis, Yong Qian, Anna A. E. Vinkhuyzen, Wei Zhao, Elizabeth G. Holliday, Andres Metspalu, Alexis C. Frazier-Wood, Meena Kumari, Nese Direk, Miriam A. Mosing, Ilja M. Nolte, Sander W. van der Laan, Matt McGue, Tim D. Spector, Marjo-Riitta Järvelin, Peter Eibich, Nancy L. Pedersen, David Schlessinger, Toshiko Tanaka, Dennis O. Mook-Kanamori, Luigi Ferrucci, Gerard Pasterkamp, Jonathan P. Beauchamp, Robert Karlsson, Lenore J. Launer, Helena Schmidt, Renée de Mutsert, Gert G. Wagner, Peter Kraft, Joseph K. Pickrell, Thorkild I. A. Sørensen, André G. Uitterlinden, Patricia A. Boyle, Cornelius A. Rietveld, Robert F. Krueger, Karl-Heinz Ladwig, Michael B. Miller, Sarah E. Medland, Tõnu Esko, Kent D. Taylor, Lavinia Paternoster, Peter J. van der Most, Richard Karlsson Linnér, Laura Pulkki-Råback, Gail Davies, Victoria Garfield, Shun-Chiao Chang, Ruifang Li-Gao, Applied Economics, Pathology, Epidemiology, Public Health, Child and Adolescent Psychiatry / Psychology, Psychiatry, Internal Medicine, Ophthalmology, Social Science Genetic Association Consortium (SSGAC), CHARGE Consortium, Okbay, Aysu, Baselmans, Bart ML, De Neve, Jan-Emmanuel, Turley, Patrick, Hyppönen, Elina, Cesarini, David, EMGO+ - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Complex Trait Genetics, Biological Psychology, Functional Genomics, Economics, Amsterdam Neuroscience - Complex Trait Genetics, Queensland Institute of Medical Research, Massachusetts General Hospital [Boston], University of Queensland [Brisbane], Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona] (UPF)-Catalunya ministerio de salud, Universitat Pompeu Fabra [Barcelona] (UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), Institut des Sciences Moléculaires (ISM), Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Université Sciences et Technologies - Bordeaux 1-Université Montesquieu - Bordeaux 4-Institut de Chimie du CNRS (INC), Tampere University Hospital, University of Turku, King‘s College London, University of Helsinki, AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Lausanne (UNIL), Birmingham City University (BCU), Helmholtz-Zentrum München (HZM), Department of Epidemiology and Public Health, University College of London [London] (UCL), Donders Institute for Brain, Cognition and Behaviour, Radboud university [Nijmegen], University of Edinburgh, Florida State University [Tallahassee] (FSU), Wuhan University [China], Rush University Medical Center [Chicago], Department of Epidemiology [Rotterdam], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Erasmus University Rotterdam, National Institute for Health and Welfare [Helsinki], Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Dpt of Pharmacology and Personalised Medicine [Maastricht], Maastricht University [Maastricht], Montpellier Research in Management (MRM), Université Montpellier 1 (UM1)-Groupe Sup de Co Montpellier (GSCM) - Montpellier Business School-Université Paul-Valéry - Montpellier 3 (UPVM)-Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Perpignan Via Domitia (UPVD), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Université Paul-Valéry - Montpellier 3 (UPVM)-Université de Perpignan Via Domitia (UPVD)-Groupe Sup de Co Montpellier (GSCM) - Montpellier Business School-Université de Montpellier (UM), Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Public Health Research (PHR), Sociology/ICS, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Stem Cell Aging Leukemia and Lymphoma (SALL), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), and LifeLines Cohort Study

Subjects
0301 basic medicine, Netherlands Twin Register (NTR), Medizin, Genome-wide association study, Disease, Genome-wide association studies, DISEASE, 0302 clinical medicine, well-being, neuroticism, Anxiety Disorders/genetics, Bayes Theorem, Depression/genetics, Genome-Wide Association Study, Humans, Phenotype, Polymorphism, Single Nucleotide, Genetics & Heredity, RISK, Genetics, PERSONALITY, [QFIN]Quantitative Finance [q-fin], Depression, HERITABILITY, COMMON VARIANTS, 11 Medical And Health Sciences, Anxiety Disorders, Neuroticism, depression, Behavioural genetics, Life Sciences & Biomedicine, Biology, personality, genetic, epidemiology, ta3111, Article, 03 medical and health sciences, SDG 3 - Good Health and Well-being, RESOURCE, Journal Article, Human height, Subjective well-being, behavioural genetics, METAANALYSIS, Genetic association, HAPPINESS, Science & Technology, MAJOR DEPRESSION, 06 Biological Sciences, Heritability, 030104 developmental biology, genome-wide association studies, HUMAN HEIGHT, 030217 neurology & neurosurgery, LifeLines Cohort Study, Developmental Biology, genome-wide analysis
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 (vertical bar(p) over cap vertical bar approximate to 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.

Published
2016

15. Genome-wide analysis identifies 12 loci influencing human reproductive behavior

Author

Ozren Polasek, Bo Jacobsson, Eleonora Porcu, Vinicius Tragante, Joel Eriksson, Jie Yao, Mika Kähönen, Mark Alan Fontana, Stefania Cappellani, J. Viikari, Rick Jansen, Crysovalanto Mamasoula, Linda Broer, Tamara B. Harris, Ellen A. Nohr, Genevieve Lachance, Johan G. Eriksson, Nicholas Eriksson, Rico Rueedi, Francesco Cucca, Jaakko Kaprio, Nicholas J. Timpson, George Dedoussis, Matt McGue, Per Magnus, Klaus Berger, Olli T. Raitakari, Cornelia M. van Duijn, Brenda W.J.H. Penninx, Jing Hua Zhao, Peter Eibich, Sheila Ulivi, Hugoline G. de Haan, Ronny Myhre, Ruth McQuillan, Florian Kronenberg, Markus Perola, Klaus Bønnelykke, Robert Karlsson, Martina La Bianca, Paul Mitchell, Ian J. Deary, Melinda Mills, Teresa Nutile, Patrick J. F. Groenen, Stacey A. Missmer, Nicholas G. Martin, Panos Deloukas, Mario Pirastu, Lindsay K. Matteson, Robert Luben, Veikko Salomaa, Renée de Mutsert, Chris Power, Nir Barzilai, Annette Kifley, Hamdi Mbarek, Denis A. Evans, Erica P. Gunderson, Tim D. Spector, Anke Tönjes, Michela Traglia, Claire Monnereau, Karin Halina Greiser, Sharon L.R. Kardia, John M. Starr, Peter K. Joshi, Sandra Lai, Doris Stöckl, James J. Lee, Heather J. Cordell, Andrew Bakshi, Nicholas J. Wareham, David C. Liewald, P Koponen, Paul M. Ridker, Joyce Y. Tung, Ilaria Gandin, Kauko Heikkilä, Johannes Haerting, Gonneke Willemsen, Janet W. Rich-Edwards, Andrew C. Heath, Astanand Jugessur, John L. Hopper, Stefan Kiechl, Henry Völzke, Daniela Ruggiero, John R. B. Perry, Dan Mellström, Simon R. Cox, Yasaman Saba, Magnus Johannesson, Ginevra Biino, David Schlessinger, Kirsi Auro, Dennis O. Mook-Kanamori, Christa Meisinger, Igor Rudan, Audrey J. Gaskins, Lars Bertram, Roy Thurik, Laura M. Yerges-Armstrong, Caterina Barbieri, Katri Räikkönen, Lawrence F. Bielak, Aviv Bergman, Philipp Koellinger, Ronald de Vlaming, Tian Liu, Johannes W. A. Smit, Peter Kovacs, Vincent W. V. Jaddoe, Jennifer A. Smith, Sven Bergmann, Inga Prokopenko, Xiuqing Guo, Marina Ciullo, Krina T. Zondervan, Marcel den Hoed, Daniel J. Benjamin, Kathryn Roll, Alan F. Wright, Helena Schmidt, William G. Iacono, Jie Jin Wang, Harold Snieder, Juho Wedenoja, Tarunveer S. Ahluwalia, David R. Weir, Ken K. Ong, Daniela Toniolo, Ruifang Li-Gao, Evelin Mihailov, Edith Hofer, Leslie J. Raffel, Daniel I. Chasman, Alexander Kluttig, Bernard Keavney, Eco J. C. de Geus, Kathleen A. Ryan, Kristin L. Ayers, Lude Franke, S. Fleur W. Meddens, Alison Pattie, Jornt J. Mandemakers, Eva Albrecht, David Cesarini, Beverley Balkau, Grant W. Montgomery, Michael Stumvoll, Ahmad Vaez, Michael B. Miller, Najaf Amin, Gyda Bjornsdottir, Cecile Lecoeur, Enes Makalic, Marc Jan Bonder, Terho Lehtimäki, Albert Hofman, Loic Yengo, Lynda M. Rose, Lisette Stolk, Juergen Wellmann, Gail Davies, Eero Kajantie, Nicole Schupf, Hans Bisgaard, Unnur Thorsteinsdottir, Konstantin Strauch, Ivana Kolcic, Lili Milani, Chunyan He, Claes Ohlsson, Yongmei Liu, Gil Atzmon, Janine F. Felix, Christian Gieger, Mike A. Nalls, Riitta Luoto, Nicola Barban, Philippe Froguel, Daniel F. Schmidt, Dorret I. Boomsma, Harry Campbell, Xia Shen, Vasiliki Lagou, Danny Ben-Avraham, Veronique Vitart, Ioanna P. Kalafati, Kari Stefansson, Daria V. Zhernakova, Constance Turman, Julie E. Buring, Johannes Waage, James F. Wilson, Maria Pina Concas, Zoltán Kutalik, Peter Willeit, Jørn Olsen, Dan Rujescu, Caroline Hayward, Penelope A. Lind, George McMahon, Elizabeth G. Holliday, Ilja M. Nolte, Fahimeh Falahi, Minh Bui, Gudmar Thorleifsson, Patrick F. McArdle, Cinzia Sala, Alana Cavadino, Rossella Sorice, Wei Zhao, Andres Metspalu, Sander W. van der Laan, Stavroula Kanoni, Elina Hyppönen, Morris A. Swertz, Simona Vaccargiu, Felix C. Tropf, Michael Lucht, Susan M. Ring, Elizabeth A. Streeten, Reinhold Schmidt, Augustine Kong, Johann Willeit, Patricia A. Peyser, Jessica D. Faul, Patrik K. E. Magnusson, Tõnu Esko, Antonietta Robino, Lavinia Paternoster, Peter J. van der Most, Kumar B. Rajan, George Davey-Smith, Dragana Vuckovic, Hans J. Grabe, Jari Lahti, Giorgia Girotto, Jorge E. Chavarro, Robert F. Krueger, Hongyan Huang, Georg Homuth, Paolo Gasparini, Sarah E. Medland, Gert G. Wagner, Peter Kraft, André G. Uitterlinden, Cornelius A. Rietveld, Howard Andrews, Cecilia M. Lindgren, Peter Vollenweider, Perry, John [0000-0001-6483-3771], Zhao, Jing Hua [0000-0003-4930-3582], Luben, Robert [0000-0002-5088-6343], Ong, Kenneth [0000-0003-4689-7530], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, BARBAN N, Rick Jansen, Ronald de Vlaming, Ahmad Vaez, Jornt J Mandemaker, Felix C Tropf, Xia Shen, James F Wilson, Daniel I Chasman, Ilja M Nolte, Vinicius Tragante, Sander W van der Laan, John R B Perry, Augustine Kong, BIOS Consortium, Tarunveer S Ahluwalia, Eva Albrecht, Laura Yerges-Armstrong, Gil Atzmon, Kirsi Auro, Kristin Ayer, Andrew Bakshi, Danny Ben-Avraham, Klaus Berger, Aviv Bergman, Lars Bertram, Lawrence F Bielak, Gyda Bjornsdottir, Marc Jan Bonder, Linda Broer, Minh Bui, Caterina Barbieri, Alana Cavadino, Jorge E Chavarro, Constance Turman, Maria Pina Conca, Heather J Cordell, Gail Davie, Peter Eibich, Nicholas Eriksson, Tõnu Esko, Joel Eriksson, Fahimeh Falahi, Janine F Felix, Mark Alan Fontana, Lude Franke, Ilaria Gandin, Audrey J Gaskin, Christian Gieger, Erica P Gunderson, Xiuqing Guo, Caroline Hayward, Chunyan He, Edith Hofer, Hongyan Huang, Peter K Joshi, Stavroula Kanoni, Robert Karlsson, Stefan Kiechl, Annette Kifley, Alexander Kluttig, Peter Kraft, Vasiliki Lagou, Cecile Lecoeur, Jari Lahti, Ruifang Li-Gao, Penelope A Lind, Tian Liu, Enes Makalic, Crysovalanto Mamasoula, Lindsay Matteson, Hamdi Mbarek, Patrick F McArdle, George McMahon, S Fleur W Medden, Evelin Mihailov, Mike Miller, Stacey A Missmer, Claire Monnereau, Peter J van der Most, Ronny Myhre, Mike A Nall, Teresa Nutile, Ioanna Panagiota Kalafati, Eleonora Porcu, Inga Prokopenko, Kumar B Rajan, Janet Rich-Edward, Cornelius A Rietveld, Antonietta Robino, Lynda M Rose, Rico Rueedi, Kathleen A Ryan, Yasaman Saba, Daniel Schmidt, Jennifer A Smith, Lisette Stolk, Elizabeth Streeten, Anke Tönje, Gudmar Thorleifsson, Sheila Ulivi, Juho Wedenoja, Juergen Wellmann, Peter Willeit, Jie Yao, Loic Yengo, Jing Hua Zhao, Wei Zhao, Daria V Zhernakova, Najaf Amin, Howard Andrew, Beverley Balkau, Nir Barzilai, Sven Bergmann, Ginevra Biino, Hans Bisgaard, Klaus Bønnelykke, Dorret I Boomsma, Julie E Buring, Harry Campbell, Stefania Cappellani, Marina Ciullo, Simon R Cox, Francesco Cucca, Daniela Toniolo, George Davey-Smith, Ian J Deary, George Dedoussi, Panos Delouka, Cornelia M van Duijn, Eco J C de Geu, Johan G Eriksson, Denis A Evan, Jessica D Faul, Cinzia Felicita Sala, Philippe Froguel, Paolo Gasparini, Giorgia Girotto, Hans-Jörgen Grabe, Karin Halina Greiser, Patrick J F Groenen, Hugoline G de Haan, Johannes Haerting, Tamara B Harri, Andrew C Heath, Kauko Heikkilä, Albert Hofman, Georg Homuth, Elizabeth G Holliday, John Hopper, Elina Hyppönen, Bo Jacobsson, Vincent W V Jaddoe, Magnus Johannesson, Astanand Jugessur, Mika Kähönen, Eero Kajantie, Sharon L R Kardia, Bernard Keavney, Ivana Kolcic, Päivikki Koponen, Peter Kovac, Florian Kronenberg, Zoltan Kutalik, Martina La Bianca, Genevieve Lachance, William G Iacono, Sandra Lai, Terho Lehtimäki, David C Liewald, LifeLines Cohort Study, Cecilia M Lindgren, Yongmei Liu, Robert Luben, Michael Lucht, Riitta Luoto, Per Magnu, Patrik K E Magnusson, Nicholas G Martin, Matt McGue, Ruth McQuillan, Sarah E Medland, Christa Meisinger, Dan Mellström, Andres Metspalu, Michela Traglia, Lili Milani, Paul Mitchell, Grant W Montgomery, Dennis Mook-Kanamori, Renée de Mutsert, Ellen A Nohr, Claes Ohlsson, Jørn Olsen, Ken K Ong, Lavinia Paternoster, Alison Pattie, Brenda W J H Penninx, Markus Perola, Patricia A Peyser, Mario Pirastu, Ozren Polasek, Chris Power, Jaakko Kaprio, Leslie J Raffel, Katri Räikkönen, Olli Raitakari, Paul M Ridker, Susan M Ring, Kathryn Roll, Igor Rudan, Daniela Ruggiero, Dan Rujescu, Veikko Salomaa, David Schlessinger, Helena Schmidt, Reinhold Schmidt, Nicole Schupf, Johannes Smit, Rossella Sorice, Tim D Spector, John M Starr, Doris Stöckl, Konstantin Strauch, Michael Stumvoll, Morris A Swertz, Unnur Thorsteinsdottir, A Roy Thurik, Nicholas J Timpson, Joyce Y Tung, André G Uitterlinden, Simona Vaccargiu, Jorma Viikari, Veronique Vitart, Henry Völzke, Peter Vollenweider, Dragana Vuckovic, Johannes Waage, Gert G Wagner, Jie Jin Wang, Nicholas J Wareham, David R Weir, Gonneke Willemsen, Johann Willeit, Alan F Wright, Krina T Zondervan, Kari Stefansson, Robert F Krueger, James J Lee, Daniel J Benjamin, David Cesarini, Philipp D Koellinger, Marcel den Hoed, Harold Snieder & Melinda C Mills, Barban, N, Jansen, R, de Vlaming, R, Vaez, A, Mandemakers, Jj, Tropf, Fc, Shen, X, Wilson, Jf, Chasman, Di, Nolte, Im, Tragante, V, van der Laan, Sw, Perry, Jr, Kong, A, Ahluwalia, T, Albrecht, E, Yerges Armstrong, L, Atzmon, G, Auro, K, Ayers, K, Bakshi, A, Ben Avraham, D, Berger, K, Bergman, A, Bertram, L, Bielak, Lf, Bjornsdottir, G, Bonder, Mj, Broer, L, Bui, M, Barbieri, CATERINA MARIA, Cavadino, A, Chavarro, Je, Turman, C, Concas, MARIA PINA, Cordell, Hj, Davies, G, Eibich, P, Eriksson, N, Esko, T, Eriksson, J, Falahi, F, Felix, Jf, Fontana, Ma, Franke, L, Gandin, Ilaria, Gaskins, Aj, Gieger, C, Gunderson, Ep, Guo, X, Hayward, C, He, C, Hofer, E, Huang, H, Joshi, Pk, Kanoni, S, Karlsson, R, Kiechl, S, Kifley, A, Kluttig, A, Kraft, P, Lagou, V, Lecoeur, C, Lahti, J, Li Gao, R, Lind, Pa, Liu, T, Makalic, E, Mamasoula, C, Matteson, L, Mbarek, H, Mcardle, Pf, Mcmahon, G, Meddens, Sf, Mihailov, E, Miller, M, Missmer, Sa, Monnereau, C, van der Most, Pj, Myhre, R, Nalls, Ma, Nutile, T, Kalafati, Ip, Porcu, E, Prokopenko, I, Rajan, Kb, Rich Edwards, J, Rietveld, Ca, Robino, Antonietta, Rose, Lm, Rueedi, R, Ryan, Ka, Saba, Y, Schmidt, D, Smith, Ja, Stolk, L, Streeten, E, Tönjes, A, Thorleifsson, G, Ulivi, Sheila, Wedenoja, J, Wellmann, J, Willeit, P, Yao, J, Yengo, L, Zhao, Jh, Zhao, W, Zhernakova, Dv, Amin, N, Andrews, H, Balkau, B, Barzilai, N, Bergmann, S, Biino, G, Bisgaard, H, Bønnelykke, K, Boomsma, Di, Buring, Je, Campbell, H, Cappellani, Stefania, Ciullo, M, Cox, Sr, Cucca, F, Toniolo, D, Davey Smith, G, Deary, Ij, Dedoussis, G, Deloukas, P, van Duijn, Cm, de Geus, Ej, Eriksson, Jg, Evans, Da, Faul, Jd, Sala, Cf, Froguel, P, Gasparini, Paolo, Girotto, Giorgia, Grabe, Hj, Greiser, Kh, Groenen, Pj, de Haan, Hg, Haerting, J, Harris, Tb, Heath, Ac, Heikkilä, K, Hofman, A, Homuth, G, Holliday, Eg, Hopper, J, Hyppönen, E, Jacobsson, B, Jaddoe, Vw, Johannesson, M, Jugessur, A, Kähönen, M, Kajantie, E, Kardia, Sl, Keavney, B, Kolcic, I, Koponen, P, Kovacs, P, Kronenberg, F, Kutalik, Z, LA BIANCA, Martina, Lachance, G, Iacono, Wg, Lai, S, Lehtimäki, T, Liewald, Dc, Lindgren, Cm, Liu, Y, Luben, R, Lucht, M, Luoto, R, Magnus, P, Magnusson, Pk, Martin, Ng, Mcgue, M, Mcquillan, R, Medland, Se, Meisinger, C, Mellström, D, Metspalu, A, Traglia, Michela, Milani, L, Mitchell, P, Montgomery, Gw, Mook Kanamori, D, de Mutsert, R, Nohr, Ea, Ohlsson, C, Olsen, J, Ong, Kk, Paternoster, L, Pattie, A, Penninx, Bw, Perola, M, Peyser, Pa, Pirastu, M, Polasek, O, Power, C, Kaprio, J, Raffel, Lj, Räikkönen, K, Raitakari, O, Ridker, Pm, Ring, Sm, Roll, K, Rudan, I, Ruggiero, D, Rujescu, D, Salomaa, V, Schlessinger, D, Schmidt, H, Schmidt, R, Schupf, N, Smit, J, Sorice, R, Spector, Td, Starr, Jm, Stöckl, D, Strauch, K, Stumvoll, M, Swertz, Ma, Thorsteinsdottir, U, Thurik, Ar, Timpson, Nj, Tung, Jy, Uitterlinden, Ag, Vaccargiu, S, Viikari, J, Vitart, V, Völzke, H, Vollenweider, P, Vuckovic, Dragana, Waage, J, Wagner, Gg, Wang, Jj, Wareham, Nj, Weir, Dr, Willemsen, G, Willeit, J, Wright, Af, Zondervan, Kt, Stefansson, K, Krueger, Rf, Lee, Jj, Benjamin, Dj, Cesarini, D, Koellinger, Pd, den Hoed, M, Snieder, H, Mills, Mc, Sociology/ICS, Life Course Epidemiology (LCE), Isotope Research, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Stem Cell Aging Leukemia and Lymphoma (SALL), Barban, Nicola, Jansen, Rick, De Vlaming, Ronald, Vaez, Ahmad, Hyppönen, Elina, Mills, Melinda C, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, EMGO - Mental health, Applied Economics, Public Health, Internal Medicine, Erasmus MC other, Epidemiology, Econometrics, Pediatrics, EMGO+ - Lifestyle, Overweight and Diabetes, Complex Trait Genetics, and Biological Psychology

Subjects
0301 basic medicine, Netherlands Twin Register (NTR), PROTEIN, WASS, Genome-wide association study, Reproductive Behavior, MOUSE, Genome-wide association studies, GWAS, reproductive behavior, fertility, 0302 clinical medicine, G1 PHASE, Pregnancy, Genetics & Heredity, Genetics, HUMAN-DISEASES, Reproduction, Human Reproduction, 11 Medical And Health Sciences, ASSOCIATION, Genome-Wide, POLYCYSTIC-OVARY-SYNDROME, Sociologie van Consumptie en Huishoudens, Parity, Phenotype, Behavioural genetics, Medical genetics, Female, BIOS Consortium, FOS: Medical biotechnology, Life Sciences & Biomedicine, Maternal Age, Infertility, medicine.medical_specialty, GENE PRIORITIZATION, Quantitative Trait Loci, Sociology of Consumption and Households, Quantitative trait locus, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, AGE, QUALITY-CONTROL, medicine, Journal Article, Life Science, SNP, Humans, gene, reproductive, behaviour, Science & Technology, ta1184, 06 Biological Sciences, medicine.disease, Genetic architecture, human reproductive behavior, 030104 developmental biology, Fertility, Human genome, Birth Order, 030217 neurology & neurosurgery, LifeLines Cohort Study, Developmental Biology, genome-wide analysis, Genome-Wide Association Study
Abstract

Barban N, Jansen R, de Vlaming R, Vaez A, Mandemakers JJ, Tropf FC, Shen X, Wilson JF, Chasman DI, Nolte IM, Tragante V, van der Laan SW, Perry JR, Kong A; BIOS Consortium, Ahluwalia TS, Albrecht E, Yerges-Armstrong L, Atzmon G, Auro K, Ayers K, Bakshi A, Ben-Avraham D, Berger K, Bergman A, Bertram L, Bielak LF, Bjornsdottir G, Bonder MJ, Broer L, Bui M, Barbieri C, Cavadino A, Chavarro JE, Turman C, Concas MP, Cordell HJ, Davies G, Eibich P, Eriksson N, Esko T, Eriksson J, Falahi F, Felix JF, Fontana MA, Franke L, Gandin I, Gaskins AJ, Gieger C, Gunderson EP, Guo X, Hayward C, He C, Hofer E, Huang H, Joshi PK, Kanoni S, Karlsson R, Kiechl S, Kifley A, Kluttig A, Kraft P, Lagou V, Lecoeur C, Lahti J, Li-Gao R, Lind PA, Liu T, Makalic E, Mamasoula C, Matteson L, Mbarek H, McArdle PF, McMahon G, Meddens SF, Mihailov E, Miller M, Missmer SA, Monnereau C, van der Most PJ, Myhre R, Nalls MA, Nutile T, Kalafati IP, Porcu E, Prokopenko I, Rajan KB, Rich-Edwards J, Rietveld CA, Robino A, Rose LM, Rueedi R, Ryan KA, Saba Y, Schmidt D, Smith JA, Stolk L, Streeten E, Tönjes A, Thorleifsson G, Ulivi S, Wedenoja J, Wellmann J, Willeit P, Yao J, Yengo L, Zhao JH, Zhao W, Zhernakova DV, Amin N, Andrews H, Balkau B, Barzilai N, Bergmann S, Biino G, Bisgaard H, Bønnelykke K, Boomsma DI, Buring JE, Campbell H, Cappellani S, Ciullo M, Cox SR, Cucca F, Toniolo D, Davey-Smith G, Deary IJ, Dedoussis G, Deloukas P, van Duijn CM, de Geus EJ, Eriksson JG, Evans DA, Faul JD, Sala CF, Froguel P, Gasparini P, Girotto G, Grabe HJ, Greiser KH, Groenen PJ, de Haan HG, Haerting J, Harris TB, Heath AC, Heikkilä K, Hofman A, Homuth G, Holliday EG, Hopper J, Hyppönen E, Jacobsson B, Jaddoe VW, Johannesson M, Jugessur A, Kähönen M, Kajantie E, Kardia SL, Keavney B, Kolcic I, Koponen P, Kovacs P, Kronenberg F, Kutalik Z, La Bianca M, Lachance G, Iacono WG, Lai S, Lehtimäki T, Liewald DC; LifeLines Cohort Study, Lindgren CM, Liu Y, Luben R, Lucht M, Luoto R, Magnus P, Magnusson PK, Martin NG, McGue M, McQuillan R, Medland SE, Meisinger C, Mellström D, Metspalu A, Traglia M, Milani L, Mitchell P, Montgomery GW, Mook-Kanamori D, de Mutsert R, Nohr EA, Ohlsson C, Olsen J, Ong KK, Paternoster L, Pattie A, Penninx BW, Perola M, Peyser PA, Pirastu M, Polasek O, Power C, Kaprio J, Raffel LJ, Räikkönen K, Raitakari O, Ridker PM, Ring SM, Roll K, Rudan I, Ruggiero D, Rujescu D, Salomaa V, Schlessinger D, Schmidt H, Schmidt R, Schupf N, Smit J, Sorice R, Spector TD, Starr JM, Stöckl D, Strauch K, Stumvoll M, Swertz MA, Thorsteinsdottir U, Thurik AR, Timpson NJ, Tung JY, Uitterlinden AG, Vaccargiu S, Viikari J, Vitart V, Völzke H, Vollenweider P, Vuckovic D, Waage J, Wagner GG, Wang JJ, Wareham NJ, Weir DR, Willemsen G, Willeit J, Wright AF, Zondervan KT, Stefansson K, Krueger RF, Lee JJ, Benjamin DJ, Cesarini D, Koellinger PD, den Hoed M, Snieder H, Mills MC.

Published
2016

16. The association between lower educational attainment and depression owing to shared genetic effects?: Results in ~25,000 subjects

Author

Patricia A. Peyser, Jessica D. Faul, Patrik K. E. Magnusson, Nicholas D. Hastie, Beate St Pourcain, Marcus Ising, Gérard Waeber, Behrooz Z. Alizadeh, Judith M. Vonk, Lawrence F. Bielak, Sang Hong Lee, Wouter J. Peyrot, Thomas Illig, M. M. Weissman, Nicholas J. Timpson, George Dedoussis, Nicholas G. Martin, Tomi E. Mäkinen, Jorma Viikari, Lili Milani, Harold Snieder, Laura J. Bierut, A. C. Heath, Reinhold E. Schmidt, Mariza de Andrade, Vilmundur Gudnason, K. Petrovic, Robert M. Kirkpatrick, Marcela González Gross, William G. Iacono, Michelle N. Meyer, Henry Völzke, Marisa Loitfelder, Maria Dimitriou, Lude Franke, Robert F. Krueger, E. J. C. G. van den Oord, Sven Cichon, Michael Conlon O'Donovan, Ian W. Craig, Shawn N. Murphy, Danielle Posthuma, Brenda W.J.H. Penninx, Aarno Palotie, Roy Thurik, Panos Deloukas, Matt McGue, M. Preisig, Patricia A. Boyle, Osorio Meirelles, Ben A. Oostra, Klaus Berger, G. M. Montgomery, Sharon L.R. Kardia, Peter K. Joshi, K. Stefansson, Paul Lichtenstein, Andrew Heath, Andrea Schulz, Dena G. Hernandez, Debbie A Lawlor, S. P. Hamilton, James B. Potash, Z. Kutalik, Elisabeth Widen, Emil L. Sigurdsson, Rudolf S N Fehrmann, Matthias Nauck, Mikael Landén, Kurt Lohman, S.D. Gordon, Lefkos T. Middleton, Caroline Hayward, Anjali K. Henders, Philipp Koellinger, Jeffrey A. Boatman, G van Grootheest, M. Daly, Jian Yang, Peter Vollenweider, Penelope A. Lind, Stacy Steinberg, Frank J. A. van Rooij, Florian Holsboer, Hkon K. Gjessing, Erkki Vartiainen, Magnus Johannesson, Jingmei Li, David Laibson, Henrik Grönberg, Tõnu Esko, Ivana Kolcic, Niina Eklund, Kelly S. Benke, Henning Tiemeier, Isaac S. Kohane, Nicolas W. Martin, Ronny Myhre, Frans G. Zitman, Arpana Agrawal, James F. Wilson, Michael R. Barnes, Lei Yu, Thorgeir E. Thorgeirsson, Franois Bastardot, Katri Räikkönen, William Lawson, Willem A. Nolen, M. Rietschel, René Breuer, Bertram Müller-Myhsok, James A. Knowles, Grant W. Montgomery, Eva Reinmaa, Rudolf Uher, Andreas Mielck, Luigi Ferrucci, S. E. Medland, Yuri Milaneschi, Philip L. De Jager, Manfred Uhr, A. E. Farmer, Cornelia M. van Duijn, Samuli Ripatti, Marja-Liisa Nuotio, Manuel Mattheisen, Sebastian E. Baumeister, David R. Van Wagoner, Martin Preisig, Fernando Rivadeneira, Peter Lichtner, Christopher Oldmeadow, Hreinn Stefansson, Ian B. Hickie, Darina Czamara, Elizabeth G. Holliday, Astanand Jugessur, Carla A. Ibrahim-Verbaas, Jaime Derringer, Vivian S. Gainer, P. Muglia, Daniel J. Benjamin, Patrick K.E. Magnusson, Patience J. Gallagher, Jennifer A. Smith, Lynn Cherkas, Pamela A. F. Madden, David A. Bennett, Zoltán Kutalik, George Davey-Smith, Gudny Eiriksdottir, Jens Treutlein, N. Craddock, Juliette Harris, Antti Latvala, Roy H. Perlis, Markus M. Noethen, Jan-Emmanuel De Neve, Stanley I. Shyn, J.H. Smit, Dalton Conley, Adriaan Hofman, Jari Lahti, Patrick J. F. Groenen, Jüri Allik, Albert V. Smith, Ozren Polasek, Susan M. Ring, Thomas Bettecken, Michele L. Pergadia, Patrick J. McGrath, Katherine E. Tansey, Stephan Ripke, Hogni Oskarsson, Peng Lin, Douglas F. Levinson, Matthijs J. H. M. van der Loos, Melissa E. Garcia, Jonathan P. Beauchamp, Rodney J. Scott, Zhihong Zhu, Michel Guipponi, Lyle J. Palmer, Alexander Teumer, William Coryell, Stefan Kloiber, Gonneke Willemsen, John Frank, Victor M. Castro, Andrew M. McIntosh, John M. Starr, Antonio Terracciano, Mika Kähönen, Marco Masala, Markus Perola, André G. Uitterlinden, Sutapa Mukherjee, Alexander Viktorin, Lenore J. Launer, Elisabeth B. Binder, William A. Scheftner, Christel M. Middeldorp, D. H. R. Blackwood, I. Jones, Thais S. Rizzi, A. Teumer, Cornelius A. Rietveld, Aldo Rustichini, Guy Lewis, Susan L. Slager, David M. Evans, Dorret I. Boomsma, Harry Campbell, Susanne Churchill, Johan G. Eriksson, Alan F. Wright, Dan V. Iosifescu, W. Maier, Francesco Cucca, Federica Tozzi, David R. Weir, Eva Albrecht, L. Milani, Jennifer R. Harris, Min A. Jhun, Marjo-Riitta Järvelin, Martin F. Elderson, Ute Bültmann, Olli T. Raitakari, Konstantin Shakhbazov, Krista Fischer, Thomas G. Schulze, T. Jung-Ying, P. Lichtenstein, Terho Lethimäki, Jeffrey B. Weilburg, Rolf Holle, Bo Jacobsson, Pedro Marques Vidal, Jordan W. Smoller, Stavroula Kanoni, Kati Kristiansson, Sergey Goryachev, Michael Steffens, Peter M. Visscher, Toshiko Tanaka, Donald J. MacIntyre, Witte J.G. Hoogendijk, David Schlessinger, Ian J. Deary, Harm-Jan Westra, Erik Ingelsson, E.J.C. de Geus, Franziska Degenhardt, Lydia Quaye, John Barnard, David C. Liewald, John P. Rice, Christopher F. Chabris, P. McGuffin, Tamara B. Harris, C. M. Lewis, Gail Davies, Enda M. Byrne, H.-Erich Wichmann, Sara Hägg, David Cesarini, Najaf Amin, Juha Karjalainen, Dale R. Nyholt, Christian Gieger, Per Hall, Ania Korszun, Neale Bm, Wei Zhao, Abdel Abdellaoui, Andres Metspalu, Christina Holzapfel, Jae Hoon Sul, Christiaan de Leeuw, Antti-Pekka Sarin, Ida Surakka, Veikko Salomaa, Mina K. Chung, N. L. Pedersen, Gerome Breen, P. A. F. Madden, Martin A. Kohli, J Kaprio, John Attia, Jing Shi, Gibran Hemani, Rauli Svento, Veronique Vitart, Susanne Lucae, L. A. Jones, Jouke-Jan Hottenga, Daniel S. Evans, Hans-Jörgen Grabe, Yongmei Liu, Danyu Lin, Albert Hofman, George McMahon, Naomi R. Wray, Stefan Herms, Stefania Bandinelli, W. Hoffmann, P.F. Sullivan, Susanne Hoefels, Michael B. Miller, Alan W. McLean, Igor Rudan, Jürgen Wellmann, Anu Realo, Maurizio Fava, Matthew Kowgier, Marika Kaakinen, Helena Schmidt, Faculteit Medische Wetenschappen/UMCG, Peyrot, WJ, Lee, SH, Milaneschi, Y, Abdellaoui, A, Penninx, BWJH, Major Depressive Disorder Working Group of the Psychiatric GWAS Consortium, Social Science Genetic Association Consortium, Psychiatry, NCA - Neurobiology of mental health, EMGO - Mental health, Applied Economics, Biological Psychology, Complex Trait Genetics, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Mental Health, Major Depressive Disorder Working Group of the Psychiatric GWAS Consortium (Corporate Collaborator), Social Science Genetic Association Consortium Corporate Collaborator, Major Depressive Disorder Working Group of the Psychiatric GWAS Consortium Corporate Collaborator, Lewis, C.M., Hamilton, S.P., Weissman, M.M., Breen, G., Blackwood, D.H., Cichon, S., Heath, A.C., Holsboer, F., Madden, P.A., McGuffin, P., Muglia, P., Pergadia, M.L., Lin, D., Müller-Myhsok, B., Steinberg, S., Grabe, H.J., Lichtenstein, P., Magnusson, P., Perlis, R.H., Preisig, M., Smoller, J.W., Stefansson, K., Uher, R., Kutalik, Z., Tansey, K.E., Teumer, A., Viktorin, A., Barnes, M.R., Bettecken, T., Binder, E.B., Breuer, R., Castro, V.M., Churchill, S.E., Coryell, W.H., Craddock, N., Craig, I.W., Czamara, D., Degenhardt, F., Farmer, A.E., Fava, M., Frank, J., Gainer, V.S., Gallagher, P.J., Gordon, S.D., Goryachev, S., Gross, M., Guipponi, M., Henders, A.K., Herms, S., Hickie, I.B., Hoefels, S., Hoogendijk, W., Iosifescu, D.V., Ising, M., Jones, I., Jones, L., Jung-Ying, T., Knowles, J.A., Kohane, I.S., Kohli, M.A., Korszun, A., Landen, M., Lawson, W.B., Lewis, G., Macintyre, D., Maier, W., Mattheisen, M., McGrath, P.J., McIntosh, A., McLean, A., Middeldorp, C.M., Middleton, L., Montgomery, G.M., Murphy, S.N., Nauck, M., Nolen, W.A., Nyholt, D.R., O'Donovan, M., Oskarsson, H., Pedersen, N., Scheftner, W.A., Schulz, A., Schulze, T.G., Shyn, S.I., Sigurdsson, E., Slager, S.L., Smit, J.H., Stefansson, H., Steffens, M., Thorgeirsson, T., Tozzi, F., Treutlein, J., Uhr, M., van den Oord, E.J., Van Grootheest, G., Völzke, H., Weilburg, J.B., Willemsen, G., Zitman, F.G., Neale, B., Daly, M., Sullivan, P.F., Agrawal, A., Albrecht, E., Alizadeh, B.Z., Allik, J., Amin, N., Attia, J.R., Bandinelli, S., Barnard, J., Bastardot, F., Baumeister, S.E., Beauchamp, J., Benjamin, D.J., Benke, K.S., Bennett, D.A., Berger, K., Bielak, L.F., Bierut, L.J., Boatman, J.A., Boyle, P.A., Bültmann, U., Campbell, H., Cesarini, D., Chabris, C.F., Cherkas, L., Chung, M.K., Conley, D., Cucca, F., Davey-Smith, G., Davies, G., de Andrade, M., De Jager, P.L., de Leeuw, C., De Neve, J.E., Deary, I.J., Dedoussis, G.V., Deloukas, P., Derringer, J., Dimitriou, M., Eiriksdottir, G., Eklund, N., Elderson, M.F., Eriksson, J.G., Evans, D.S., Evans, D.M., Faul, J.D., Fehrmann, R., Ferrucci, L., Fischer, K., Franke, L., Garcia, M.E., Gieger, C., Gjessing, H.K., Groenen, P.J., Grönberg, H., Gudnason, V., Hägg, S., Hall, P., Harris, J.R., Harris, J.M., Harris, T.B., Hastie, N.D., Hayward, C., Hernandez, D.G., Hoffmann, W., Hofman, A., Holle, R., Holliday, E.G., Holzapfel, C., Iacono, W.G., Ibrahim-Verbaas, C.A., Illig, T., Ingelsson, E., Jacobsson, B., Järvelin, M.R., Jhun, M.A., Johannesson, M., Joshi, P.K., Jugessur, A., Kaakinen, M., Kähönen, M., Kanoni, S., Kaprio, J., Kardia, S.L., Karjalainen, J., Kirkpatrick, R.M., Koellinger, P.D., Kolcic, I., Kowgier, M., Kristiansson, K., Krueger, R.F., Lahti, J., Laibson, D., Latvala, A., Launer, L.J., Lawlor, D.A., Lethimäki, T., Li, J., Lichtner, P.K., Liewald, D.C., Lin, P., Lind, P.A., Liu, Y., Lohman, K., Loitfelder, M., Magnusson, P.K., Mäkinen, T.E., Vidal, P.M., Martin, N.W., Masala, M., McGue, M., McMahon, G., Meirelles, O., Meyer, M.N., Mielck, A., Milani, L., Miller, M.B., Montgomery, G.W., Mukherjee, S., Myhre, R., Nuotio, M.L., Oldmeadow, C.J., Oostra, B.A., Palmer, L.J., Palotie, A., Perola, M., Petrovic, K.E., Peyser, P.A., Polašek, O., Posthuma, D., Quaye, L., Räikkönen, K., Raitakari, O.T., Realo, A., Reinmaa, E., Rice, J.P., Ring, S.M., Ripatti, S., Rivadeneira, F., Rizzi, T.S., Rudan, I., Rustichini, A., Salomaa, V., Sarin, A.P., Schlessinger, D., Schmidt, H., Schmidt, R., Scott, R.J., Shakhbazov, K., Smith, A.V., Smith, J.A., Snieder, H., Pourcain, B.S., Starr, J.M., Sul, J.H., Surakka, I., Svento, R., Tanaka, T., Terracciano, A., Thurik, A.R., Tiemeier, H., Timpson, N.J., Uitterlinden, A.G., van der Loos, M.J., van Duijn, C.M., van Rooij, F.J., Van Wagoner, D.R., Vartiainen, E., Viikari, J., Visscher, P.M., Vitart, V., Vollenweider, P.K., Vonk, J.M., Waeber, G., Weir, D.R., Wellmann, J., Westra, H.J., Wichmann, H.E., Widen, E., Wilson, J.F., Wright, A.F., Yang, J., Yu, L., and Zhao, W.

Subjects
Netherlands Twin Register (NTR), Male, Genome-wide association study, Logistic regression, Cohort Studies, Odds Ratio, pleiotropic genetic effects, Netherlands, Psychiatry, education.field_of_study, Likelihood Functions, Single Nucleotide, Middle Aged, Psychiatry and Mental health, educational attainment, depression, Major depressive disorder, Educational Status, Regression Analysis, Female, Psychology, Adult, Estonia, medicine.medical_specialty, Biochemistry & Molecular Biology, Aged, Depressive Disorder, Major/epidemiology, Depressive Disorder, Major/genetics, Depressive Disorder, Major/psychology, Estonia/epidemiology, Gene-Environment Interaction, Genetic Association Studies, Genotype, Humans, Netherlands/epidemiology, Polymorphism, Single Nucleotide/genetics, Psychiatric Status Rating Scales, Concordance, Population, SNP, Single-nucleotide polymorphism, Genetic correlation, behavioral disciplines and activities, Polymorphism, Single Nucleotide, Article, Cellular and Molecular Neuroscience, mental disorders, medicine, Polymorphism, education, Molecular Biology, Depressive Disorder, Depressive Disorder, Major, major depressive disorder, ta1184, Neurosciences, Major, Odds ratio, medicine.disease, ta3124, Neurosciences & Neurology, polymorphisms, Demography
Abstract

An association between lower educational attainment (EA) and an increased risk for depression has been confirmed in various western countries. This study examines whether pleiotropic genetic effects contribute to this association. Therefore, data were analyzed from a total of 9662 major depressive disorder (MDD) cases and 14 949 controls (with no lifetime MDD diagnosis) from the Psychiatric Genomics Consortium with additional Dutch and Estonian data. The association of EA and MDD was assessed with logistic regression in 15 138 individuals indicating a significantly negative association in our sample with an odds ratio for MDD 0.78 (0.75-0.82) per standard deviation increase in EA. With data of 884 105 autosomal common single-nucleotide polymorphisms (SNPs), three methods were applied to test for pleiotropy between MDD and EA: (i) genetic profile risk scores (GPRS) derived from training data for EA (independent meta-analysis on similar to 120 000 subjects) and MDD (using a 10-fold leave-one-out procedure in the current sample), (ii) bivariate genomic-relationship-matrix restricted maximum likelihood (GREML) and (iii) SNP effect concordance analysis (SECA). With these methods, we found (i) that the EA-GPRS did not predict MDD status, and MDD-GPRS did not predict EA, (ii) a weak negative genetic correlation with bivariate GREML analyses, but this correlation was not consistently significant, (iii) no evidence for concordance of MDD and EA SNP effects with SECA analysis. To conclude, our study confirms an association of lower EA and MDD risk, but this association was not because of measurable pleiotropic genetic effects, which suggests that environmental factors could be involved, for example, socioeconomic status. Refereed/Peer-reviewed

Published
2015

17. Polygenic risk scores for schizophrenia and bipolar disorder predict creativity

Author

Agnar Helgason, Robert Power, Fredrik Ullén, Patrik K. E. Magnusson, Augustine Kong, Frank J. A. van Rooij, Henning Tiemeier, Dorret I. Boomsma, Thorgeir E. Thorgeirsson, Gyda Bjornsdottir, Michel M Nivard, Jouke J. Hottenga, Lambertus A. Kiemeney, Abdel Abdellaoui, David Cesarini, Magnus Johannesson, Engilbert Sigurdsson, Philipp Koellinger, Cornelius A. Rietveld, Andres Ingason, Stacy Steinberg, G. Bragi Walters, Daniel F. Gudbjartsson, Gonneke Willemsen, Hreinn Stefansson, Tessel E. Galesloot, Kari Stefansson, Albert Hofman, Daniel J. Benjamin, [ 1 ] deCODE Genet Amgen, Reykjavik, Iceland [ 2 ] Kings Coll London, Inst Psychiat, Genet & Dev Psychiat Ctr, MRC Social, London WC2R 2LS, England [ 3 ] Erasmus Univ, Erasmus Sch Econ, Rotterdam, Netherlands [ 4 ] Vrije Univ Amsterdam, Dept Biol Psychol, Netherlands Twin Register, Amsterdam, Netherlands [ 5 ] Stockholm Sch Econ, Dept Econ, Stockholm, Sweden [ 6 ] Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Nijmegen, Netherlands [ 7 ] Ctr Expt Social Sci, New York, NY USA [ 8 ] Univ So Calif, Ctr Econ & Social Res, Los Angeles, CA USA [ 9 ] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden [ 10 ] Karolinska Inst, Dept Neurosci, Stockholm, Sweden [ 11 ] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands [ 12 ] Landspitali Univ Hosp, Dept Psychiat, Reykjavik, Iceland [ 13 ] Univ Iceland, Dept Anthropol, Reykjavik, Iceland [ 14 ] Univ Amsterdam, Fac Econ & Business, Amsterdam, Netherlands, Applied Economics, Epidemiology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Mental Health, Biological Psychology, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, and Complex Trait Genetics

Subjects
Netherlands Twin Register (NTR), Sköpunargáfa, medicine.medical_specialty, Psychosis, Multifactorial Inheritance, Bipolar Disorder, media_common.quotation_subject, Genome-wide association study, Creativity, 03 medical and health sciences, 0302 clinical medicine, Geðklofi, mental disorders, medicine, Bipolar disorder, Psychiatry, media_common, Geðhvarfasýki, Extramural, General Neuroscience, Arfgengi, medicine.disease, 3. Good health, 030227 psychiatry, Schizophrenia, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Polygenic risk score, Psychology, 030217 neurology & neurosurgery, Clinical psychology, Cohort study
Abstract

To access publisher's full text version of this article click on the hyperlink at the bottom of the page We tested whether polygenic risk scores for schizophrenia and bipolar disorder would predict creativity. Higher scores were associated with artistic society membership or creative profession in both Icelandic (P = 5.2 × 10(-6) and 3.8 × 10(-6) for schizophrenia and bipolar disorder scores, respectively) and replication cohorts (P = 0.0021 and 0.00086). This could not be accounted for by increased relatedness between creative individuals and those with psychoses, indicating that creativity and psychosis share genetic roots. Innovative Medicines Initiative 115008 European Union GA 286213 National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust King's College London Netherlands Organisation for Scientific Research NWO Investments 175.010.2005.011 911-03-012 Research Institute for Diseases in the Elderly 014-93-015 RIDE2 Netherlands Genomics Initiative (NGI)/Netherlands Consortium for Healthy Aging (NCHA) 050-060-810 Erasmus Medical Center Erasmus University, Rotterdam Netherlands Organization for the Health Research and Development (ZonMw) Research Institute for Diseases in the Elderly (RIDE) Ministry of Education, Culture, and Science Ministry for Health, Welfare, and Sports European Commission (DG XII) Municipality of Rotterdam Netherlands Organization for Scientific Research (NWO) MagW/ZonMW BBMRI-NL 184.021.007 VU University Institute for Health and Care Research (EMGO+) Neuroscience Campus Amsterdam European Science Council (ERC) Genetics of Mental Illness 230374 Avera Institute for Human Genetics and US National Institute of Mental Health 1RC2MH089951-01 1RC2 MH089995 Ragnar Soderberg Foundation E9/11 Swedish Research Council 421-2013-1061 Jan Wallander and Tom Hedelius Foundation P2012-0002:1 Sven and Dagmar Salen Foundation Bank of Sweden Tercentenary Foundation M11-0451:1 Karolinska Institutet Netherlands Scientific Organization NWO 480-05-003 info:eu-repo/grantAgreement/EC/FP7/286213

Published
2015

18. Common genetic variants associated with cognitive performance identified using the proxy-phenotype method

Author

Magnus Johannesson, André G. Uitterlinden, Cornelius A. Rietveld, Nicholas J. Timpson, Sarah E. Medland, Tõnu Esko, Beben Benyamin, Ian J. Deary, Sven J. van der Lee, Christiaan de Leeuw, Nicholas G. Martin, Matt McGue, Cornelia M. van Duijn, David C. Liewald, Patrick Turley, Nancy L. Pedersen, Paul Lichtenstein, Jaime Derringer, Frank C. Verhulst, James J. Lee, Carla A. Ibrahim-Verbaas, Dalton Conley, Philipp Koellinger, John M. Starr, Tune H. Pers, Christopher F. Chabris, David Cesarini, David Laibson, Edward L. Glaeser, Najaf Amin, Olga Rostapshova, Maciej Trzaskowski, Juha Karjalainen, Mary E. Ward, Caroline Hayward, Valur Emilsson, Patrik K. E. Magnusson, Henning Tiemeier, Daniel J. Benjamin, Robert Plomin, David J. Porteous, George Davey Smith, Michael B. Miller, Margaret J. Wright, Fernando Rivadeneira, Vincent W. V. Jaddoe, Anna A. E. Vinkhuyzen, William G. Iacono, Lude Franke, Peter M. Visscher, Rudolf S N Fehrmann, Gail Davies, Andrew D. Johnson, Steven Pinker, Riccardo E. Marioni, Blair H. Smith, George McMahon, Danielle Posthuma, Narelle K. Hansell, Human genetics, NCA - Brain mechanisms in health and disease, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, Functional Genomics, Complex Trait Genetics, Tinbergen Institute, Amsterdam Neuroscience - Complex Trait Genetics, Rietveld, Cornelius A, Esko, Tõnu, Davies, Gail, Pers, Tune H, Benyamin, Beben, Koellinger, Philipp D, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Stem Cell Aging Leukemia and Lymphoma (SALL), Entrepreneurship & Innovation (ABS, FEB), Epidemiology, Erasmus MC other, Child and Adolescent Psychiatry / Psychology, and Internal Medicine

Subjects
Male, Multifactorial Inheritance, Cell Adhesion Molecules, Neuronal, LOCI, Social Sciences, Single-nucleotide polymorphism, Genome-wide association study, INTELLIGENCE, Nerve Tissue Proteins, Biology, Polymorphism, Single Nucleotide, Synaptic Transmission, Corrections, Cognition, Memory, medicine, ACADEMIC-ACHIEVEMENT, Dementia, GWAS, Humans, Learning, Effects of sleep deprivation on cognitive performance, GENOME-WIDE ASSOCIATION, Neural Cell Adhesion Molecules, Genetics, Multidisciplinary, Neuronal Plasticity, proxy-phenotype method, Memoria, COMPONENTS, Calcium-Binding Proteins, medicine.disease, Multiple comparisons problem, Octamer Transcription Factors, Female, SDG 4 - Quality Education
Abstract

We identify common genetic variants associated with cognitive performance using a two-stage approach, which we call the proxyphenotype 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. Refereed/Peer-reviewed

Published
2014

19. WHO IS ‘BEHAVIORAL’? COGNITIVE ABILITY AND ANOMALOUS PREFERENCES

Author

Daniel J. Benjamin, Sebastian A. Brown, and Jesse M. Shapiro

Subjects
education, Article
Abstract

In this paper, we ask whether variation in preference anomalies is related to variation in cognitive ability. Evidence from a new laboratory study of Chilean high-school students with similar schooling backgrounds shows that small-stakes risk aversion and short-run discounting are less common among those with higher standardized test scores. The relationship with test scores survives controls for parental education and wealth. We find some evidence that elementary-school GPA is predictive of preferences measured at the end of high school. Two laboratory interventions provide suggestive evidence of a possible causal impact of cognitive resources on expressed preferences. (JEL: J24, D14, C91).

Published
2013

20. Why It Is Hard to Find Genes Associated With Social Science Traits: Theoretical and Empirical Considerations

Author

Steven Pinker, David Laibson, Daniel J. Benjamin, James J. Lee, Grégoire Borst, Christopher F. Chabris, Edward L. Glaeser, Jonathan P. Beauchamp, Center of Excellence in Neuroscience, CHU de Montréal, Fraunhofer Institute for Process Engineering and Packaging (Fraunhofer IVV), Fraunhofer (Fraunhofer-Gesellschaft), Laboratoire de psychologie du développement et de l'éducation de l'enfant (LaPsyDÉ - UMR 8240), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Department of Psychology, and Harvard University [Cambridge]

Subjects
Adult, Male, Candidate gene, Genetic Research, Adolescent, Research and Practice, media_common.quotation_subject, Social Sciences, Genome-wide association study, Polymorphism, Single Nucleotide, 03 medical and health sciences, Young Adult, [SCCO]Cognitive science, 0302 clinical medicine, Surveys and Questionnaires, Humans, Allele, Social science, Selection, Genetic, Hair Color, Selection (genetic algorithm), ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, media_common, Biological Phenomena, Selection bias, 0303 health sciences, Behavior, Natural selection, Eye Color, Directional selection, [SCCO.NEUR]Cognitive science/Neuroscience, Public Health, Environmental and Occupational Health, Genetic architecture, Genes, [SCCO.PSYC]Cognitive science/Psychology, Female, 030217 neurology & neurosurgery, Genome-Wide Association Study, Personality
Abstract

Objectives. We explain why traits of interest to behavioral scientists may have a genetic architecture featuring hundreds or thousands of loci with tiny individual effects rather than a few with large effects and why such an architecture makes it difficult to find robust associations between traits and genes. Methods. We conducted a genome-wide association study at 2 sites, Harvard University and Union College, measuring more than 100 physical and behavioral traits with a sample size typical of candidate gene studies. We evaluated predictions that alleles with large effect sizes would be rare and most traits of interest to social science are likely characterized by a lack of strong directional selection. We also carried out a theoretical analysis of the genetic architecture of traits based on R.A. Fisher’s geometric model of natural selection and empirical analyses of the effects of selection bias and phenotype measurement stability on the results of genetic association studies. Results. Although we replicated several known genetic associations with physical traits, we found only 2 associations with behavioral traits that met the nominal genome-wide significance threshold, indicating that physical and behavioral traits are mainly affected by numerous genes with small effects. Conclusions. The challenge for social science genomics is the likelihood that genes are connected to behavioral variation by lengthy, nonlinear, interactive causal chains, and unraveling these chains requires allying with personal genomics to take advantage of the potential for large sample sizes as well as continuing with traditional epidemiological studies.

Published
2013

21. The Molecular Genetic Architecture of Self-Employment

Author

Albert V. Smith, Magnus Johannesson, Emmi Tikkanen, Birgit Höhne, Johan G. Eriksson, Georgina A. Ankra-Badu, Jari Lahti, Francesco Cucca, Dorret I. Boomsma, Silvia Naitza, Vilmundur Gudnason, Olli T. Raitakari, Stefan Blankenberg, George Dedoussis, Philipp S. Wild, Rolf Holle, Aaron Isaacs, Panos Deloukas, André G. Uitterlinden, Paul Scheet, Marika Kaakinen, Helena Schmidt, Ida Surakka, Philipp Koellinger, Marisa Loitfelder, Cornelius A. Rietveld, Ben A. Oostra, David Cesarini, Rauli Svento, Antonio Terracciano, Stavroula Kanoni, Christian Gieger, Henry Völzke, Markus Perola, Gonçalo R. Abecasis, Albert Hofman, Lenore J. Launer, Andrea Senft, Roy Thurik, Matthijs J. H. M. van der Loos, Patrik K. E. Magnusson, Tim D. Spector, Maarit A. Laaksonen, Sebastian E. Baumeister, Jorma Viikari, Lydia Quaye, Sara M. Willems, Frank J. A. van Rooij, Marjo-Riitta Järvelin, Jouke-Jan Hottenga, Reiner Biffar, David Schlessinger, Niina Eklund, Carsten Oliver Schmidt, Maria Dimitriou, Cornelia M. van Duijn, Samuli Ripatti, Mika Kähönen, Reinhold Schmidt, Fernando Rivadeneira, Gudny Eiriksdottir, Patrick J. F. Groenen, Katja Petrovic, Gonneke Willemsen, Eco J. C. de Geus, H.-Erich Wichmann, Terho Lehtimäki, Daniel J. Benjamin, Applied Economics, Erasmus School of Economics, Internal Medicine, Epidemiology, Clinical Genetics, Econometrics, Institute for Molecular Medicine Finland, Clinicum, Department of General Practice and Primary Health Care, Behavioural Sciences, Hjelt Institute (-2014), Diabetes and Obesity Research Program, Biostatistics Helsinki, Quantitative Genetics, Developmental Psychology Research Group, Complex Disease Genetics, ABS Other Research (FEB), Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Mental Health, Neuroscience Campus Amsterdam - Brain Imaging Technology, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, Tinbergen Institute, Amsterdam Neuroscience - Complex Trait Genetics, Biological Psychology, and Management and Organisation

Subjects
Male, Netherlands Twin Register (NTR), Multifactorial Inheritance, Heredity, Epidemiology, Economics, Intelligence, Twins, Genome-wide association study, CORONARY HEART-DISEASE, Social and Behavioral Sciences, Theoretical, Missing heritability problem, Models, MISSING HERITABILITY, Microeconomics, Twins, Dizygotic, SOCIOECONOMIC-STATUS, Registries, Genetics, 0303 health sciences, Multidisciplinary, Statistics, 05 social sciences, Genomics, Single Nucleotide, Occupational and Industrial Health, 3. Good health, CARDIOVASCULAR-DISEASE, Genetic Epidemiology, Meta-analysis, Science & Technology - Other Topics, Medicine, Female, Public Health, Behavioral and Social Aspects of Health, Research Article, Personality, Employment, Genotype, Clinical Research Design, General Science & Technology, 515 Psychology, Science, education, Single-nucleotide polymorphism, Biostatistics, Biology, Polymorphism, Single Nucleotide, Monozygotic, 03 medical and health sciences, Genome Analysis Tools, 0502 economics and business, MD Multidisciplinary, Genome-Wide Association Studies, Dizygotic, Humans, Statistical Methods, Human height, Polymorphism, GENOME-WIDE ASSOCIATION, 030304 developmental biology, Genetic association, EDUCATIONAL-ATTAINMENT, Science & Technology, Complex Traits, MULTIDISCIPLINARY SCIENCES, Computational Biology, Human Genetics, SDG 8 - Decent Work and Economic Growth, Twins, Monozygotic, ta3121, Heritability, Models, Theoretical, Genetic architecture, COMMON SNPS EXPLAIN, LARGE PROPORTION, Genetic Polymorphism, RISK-FACTORS, Gene-Environment Interaction, 3111 Biomedicine, Meta-Analyses, HUMAN HEIGHT, Population Genetics, Mathematics, 050203 business & management, Genome-Wide Association Study
Abstract

Economic variables such as income, education, and occupation are known to affect mortality and morbidity, such as cardiovascular disease, and have also been shown to be partly heritable. However, very little is known about which genes influence economic variables, although these genes may have both a direct and an indirect effect on health. We report results from the first large-scale collaboration that studies the molecular genetic architecture of an economic variable-entrepreneurship-that was operationalized using self-employment, a widely-available proxy. Our results suggest that common SNPs when considered jointly explain about half of the narrow-sense heritability of self-employment estimated in twin data (σg (2)/σP (2) = 25%, h (2) = 55%). However, a meta-analysis of genome-wide association studies across sixteen studies comprising 50,627 participants did not identify genome-wide significant SNPs. 58 SNPs with p

Published
2013

22. GWAS of 126559 Individuals Identifies Genetic Variants Associated with Educational Attainment

Author

Maria Dimitriou, Klaus Berger, Jian Yang, Nicholas J. Timpson, George Dedoussis, Magnus Johannesson, Igor Rudan, Marisa Loitfelder, Kurt Lohman, Jürgen Wellmann, Osorio Meirelles, Johan G. Eriksson, Cornelia M. van Duijn, Francesco Cucca, Anu Realo, Gérard Waeber, David R. Van Wagoner, Samuli Ripatti, Alan F. Wright, George McMahon, Elizabeth G. Holliday, Lili Milani, Ute Bültmann, Olli T. Raitakari, Behrooz Z. Alizadeh, Reinhold Schmidt, Matthew Kowgier, André G. Uitterlinden, Sutapa Mukherjee, William G. Iacono, Judith M. Vonk, Lude Franke, John M. Starr, Antonio Terracciano, Rudolf Ferhmann, Pamela A. F. Madden, Marika Kaakinen, Helena Schmidt, Dorret I. Boomsma, Harry Campbell, Konstantin Shakhbazov, Lei Yu, Albert Hofman, Tõnu Esko, Cornelius A. Rietveld, Albert V. Smith, Arpana Agrawal, Wouter J. Peyrot, Stefania Bandinelli, David M. Evans, Nicolas W. Martin, Martin F. Elderson, Melissa E. Garcia, Danielle Posthuma, Ozren Polasek, Panos Deloukas, Pedro Marques Vidal, Sang Hong Lee, James F. Wilson, Robert F. Krueger, Paul Lichtenstein, Jan-Emmanuel De Neve, Fernando Rivadeneira, Laura J. Bierut, Sebastian E. Baumeister, Lawrence F. Bielak, Peter M. Visscher, Philipp Koellinger, Thais S. Rizzi, Rodney J. Scott, Mika Kähönen, Marco Masala, Debbie A Lawlor, Yongmei Liu, Ben A. Oostra, Jaime Derringer, Zoltán Kutalik, Carla A. Ibrahim-Verbaas, Toshiko Tanaka, Håkon K. Gjessing, Jae Hoon Sul, Marjo-Riitta Järvelin, Krista Fischer, Erik Ingelsson, David R. Weir, Kati Kristiansson, Thomas Illig, Jorma Viikari, George Davey-Smith, Antti-Pekka Sarin, Matt McGue, Ida Surakka, Andreas Mielck, Ivana Kolcic, Astanand Jugessur, Aldo Rustichini, Sarah E. Medland, Ronny Myhre, Veikko Salomaa, Mina K. Chung, H.-Erich Wichmann, Lynn Cherkas, Peter Lichtner, Michael B. Miller, Peter Vollenweider, Jüri Allik, Henning Tiemeier, Grant W. Montgomery, Eva Reinmaa, Dalton Conley, Adriaan Hofman, Patricia A. Peyser, David Schlessinger, Martin Preisig, Jessica D. Faul, Patrik K. E. Magnusson, David A. Bennett, Erkki Vartiainen, David Laibson, François Bastardot, Niina Eklund, Wolfgang Hoffmann, Terho Lehtimäki, Nicholas D. Hastie, John P. Rice, Rolf Holle, Antti Latvala, Guoný Eiríksdóttir, Luigi Ferrucci, Jennifer A. Smith, Christian Gieger, Veronique Vitart, Gail Davies, Sara Hägg, Juha Karjalainen, Matthijs J. H. M. van der Loos, Bo Jacobsson, Lydia Quaye, John Barnard, Beate St Pourcain, Jouke-Jan Hottenga, Daniel S. Evans, Jonathan P. Beauchamp, Tamara B. Harris, Ian J. Deary, Jari Lahti, Peng Lin, Markus Perola, Henry Völzke, Lenore J. Launer, David C. Liewald, Brenda W.J.H. Penninx, David Cesarini, Najaf Amin, Dale R. Nyholt, Roy Thurik, Aarno Palotie, Patrick J. F. Groenen, Elisabeth Widen, Caroline Hayward, Penelope A. Lind, Susan M. Ring, Lyle J. Palmer, Alexander Teumer, Kelly S. Benke, Christopher Oldmeadow, Katja Petrovic, Gonneke Willemsen, Andrew C. Heath, Harold Snieder, Jaakko Kaprio, Marja-Liisa Nuotio, Frank J. A. van Rooij, Robert M. Kirkpatrick, Nicholas G. Martin, Tomi E. Mäkinen, Michelle N. Meyer, Katri Räikkönen, Harm-Jan Westra, Daniel J. Benjamin, Jeffrey A. Boatman, Henrik Grönberg, Eva Albrecht, Sharon L.R. Kardia, Peter K. Joshi, Philip L. De Jager, Mariza de Andrade, Patricia A. Boyle, Jennifer R. Harris, Vilmundur Guonason, Christiaan de Leeuw, Juliette Harris, Dena G. Hernandez, Jingmei Li, Per Hall, Wei Zhao, Abdel Abdellaoui, Andres Metspalu, Christina Holzapfel, Stavroula Kanoni, Christopher F. Chabris, John Attia, Rauli Svento, Erasmus School of Economics, Epidemiology, Surgery, Neurology, Applied Economics, Research Methods and Techniques, Clinical Genetics, Internal Medicine, Child and Adolescent Psychiatry / Psychology, Econometrics, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Lifestyle, Overweight and Diabetes, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, Biological Psychology, Functional Genomics, Management and Organisation, Tinbergen Institute, Amsterdam Neuroscience - Complex Trait Genetics, Rietveld, Cornelius A, Medland, Sarah E, Derringer, Jaime, Yang, Jian, Lee, Sang Hong, Koellinger, Philipp D, LifeLines Cohort Study, ABS Other Research (FEB), Reproductive Origins of Adult Health and Disease (ROAHD), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Life Course Epidemiology (LCE), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Public Health Research (PHR), Teaching and Teacher Education, Groningen Research Institute for Asthma and COPD (GRIAC), Stem Cell Aging Leukemia and Lymphoma (SALL), Psychiatry, Human genetics, NCA - Brain mechanisms in health and disease, NCA - Neurobiology of mental health, and EMGO - Lifestyle, overweight and diabetes

Subjects
Netherlands Twin Register (NTR), Male, medicine.medical_specialty, Multifactorial Inheritance, Endophenotypes, social-science genetics, LOCI, SNP, Single-nucleotide polymorphism, Genome-wide association study, Biology, PREFERENCES, Polymorphism, Single Nucleotide, 03 medical and health sciences, 0302 clinical medicine, Cognition, Polymorphism (computer science), medicine, GWAS, Humans, Allele, Polymorphism, education, gene, attainment, 030304 developmental biology, Genetics, 0303 health sciences, ENVIRONMENT, genome-wide association study, Multidisciplinary, Data Science, Replicate, Single Nucleotide, single-nucleotide polymorphism, linear polygenic score, ta3121, Educational attainment, Multidisciplinary Sciences, Educational Status, Female, Genetic Loci, Genome-Wide Association Study, educational attainment, Endophenotype, Medical genetics, 030217 neurology & neurosurgery
Abstract

Genetic College Many genomic elements in humans are associated with behavior, including educational attainment. In a genome-wide association study including more than 100,000 samples, Rietveld et al. (p. 1467 , published online 30 May; see the Perspective by Flint and Munafò ) looked for genes related to educational attainment in Caucasians. Small genetic effects at three loci appeared to impact educational attainment.

Published
2013

23. Social Identity and Preferences*

Author

James J. Choi, A. Joshua Strickland, and Daniel J. Benjamin

Subjects
Economics and Econometrics, jel:D81, jel:Z13, 050208 finance, Gender identity, jel:C91, Risk aversion, media_common.quotation_subject, 05 social sciences, Immigration, Ethnic group, Identity (social science), Article, 5. Gender equality, Salient, 0502 economics and business, jel:J15, Economics, Economic anthropology, jel:J16, 050207 economics, jel:Z10, Social identity theory, Social psychology, media_common
Abstract

Social identities prescribe behaviors for people. We identify the marginal behavioral effect of these norms on discount rates and risk aversion by measuring how laboratory subjects' choices change when an aspect of social identity is made salient. When we make ethnic identity salient to Asian-American subjects, they make more patient choices. When we make racial identity salient to black subjects, non-immigrant blacks (but not immigrant blacks) make more patient choices. Making gender identity salient has no effect on intertemporal or risk choices. (JEL D81, J15, J16, Z13)

Published
2010

24. Consensus-based guidance for conducting and reporting multi-analyst studies

Author

Casper J. Albers, Daniel J. Simons, Michael Kirchler, Brian A Nosek, Alexander T. Kindel, David R. Shanks, Morton Ann Gernsbacher, Tom Schonberg, Russell A. Poldrack, Nelson Cowan, Martin Schweinsberg, Juergen Huber, Barbara A. Spellman, Eric Luis Uhlmann, Dora Matzke, Yoram K. Kunkels, Udo Boehm, Laura F. Bringmann, D. Stephen Lindsay, Kai J. Jonas, Gilles Dutilh, Noah van Dongen, Daniel J. Benjamin, Johnny van Doorn, Magnus Johannesson, Andrea M Cataldo, Alexandra Sarafoglou, Don van Ravenzwaaij, Barnabas Szaszi, Matthew J. Salganik, Felix Holzmeister, Andrew Delios, Anna Dreber, Balazs Aczel, Olmo van den Akker, Raphael Silberzahn, Jean-François Mangin, Niko A. Busch, Jelte M. Wicherts, Chris Donkin, Jojanneke A. Bastiaansen, Marcel A.L.M. van Assen, Rink Hoekstra, Samuel St-Jean, Ben R. Newell, Jörg Rieskamp, Marcus R. Munafò, Gary F. Egan, Jeffrey J. Starns, Gustav Nilsonne, Eric-Jan Wagenmakers, Emmanuel Caruyer, Sabine Hoffmann, Rotem Botvinik-Nezer, Caruyer, Emmanuel, Eötvös Loránd University (ELTE), Karolinska Institutet [Stockholm], Tilburg University [Tilburg], Netspar, University of Groningen [Groningen], University of Southern California (USC), University of Amsterdam [Amsterdam] (UvA), Dartmouth College [Hanover], Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Neuroimagerie: méthodes et applications (Empenn), Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-SIGNAUX ET IMAGES NUMÉRIQUES, ROBOTIQUE (IRISA-D5), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), McLean Hospital [Belmont, Ma.], University of Missouri [Columbia] (Mizzou), University of Missouri System, National University of Singapore (NUS), University of New South Wales [Sydney] (UNSW), Stockholm School of Economics (SSE), University Hospital Basel [Basel], Monash University [Melbourne], University of Wisconsin-Madison, Ludwig-Maximilians-Universität München (LMU), Leopold Franzens Universität Innsbruck - University of Innsbruck, Maastricht University [Maastricht], Princeton University, University of Victoria [Canada] (UVIC), Université Paris-Saclay, University of Bristol [Bristol], University of Virginia, Stanford University, University of Basel (Unibas), Tel Aviv University (TAU), European School of Management and Technology [Berlin, Germany] (ESMT), University College of London [London] (UCL), University of Sussex, University of Illinois at Urbana-Champaign [Urbana], University of Illinois System, University of Alberta, University of Massachusetts [Amherst] (UMass Amherst), University of Massachusetts System (UMASS), Institut européen d'administration des affaires [Singapour, Singapour] (INSEAD), University of Münster, Université de Rennes (UNIV-RENNES), University of Innsbruck, University of Virginia [Charlottesville], Tel Aviv University [Tel Aviv], Department of Methodology and Statistics, Empenn, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes 1 (UR1), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Psychometrics and Statistics, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), and Research and Evaluation of Educational Effectiveness

Subjects
Data Analysis, Consensus, medicine, QH301-705.5, Computer science, none, Science, Datasets as Topic, statistical practice, Machine learning, computer.software_genre, General Biochemistry, Genetics and Molecular Biology, neuroscience, 03 medical and health sciences, 0302 clinical medicine, Science Forum, REPRODUCIBILITY, multi-analyst, Applied research, Biology (General), Robustness (economics), 030304 developmental biology, DELPHI, 0303 health sciences, metascience, expert consensus, General Immunology and Microbiology, business.industry, General Neuroscience, Research, [SCCO.NEUR]Cognitive science/Neuroscience, Feature Article, [SCCO.NEUR] Cognitive science/Neuroscience, Expert consensus, General Medicine, science forum, Artificial intelligence, Biochemistry and Cell Biology, analytical variability, business, computer, 030217 neurology & neurosurgery
Abstract

International audience; Any large dataset can be analyzed in a number of ways, and it is possible that the use of different analysis strategies will lead to different results and conclusions. One way to assess whether the results obtained depend on the analysis strategy chosen is to employ multiple analysts and leave each of them free to follow their own approach. Here, we present consensus-based guidance for conducting and reporting such multi-analyst studies, and we discuss how broader adoption of the multi-analyst approach has the potential to strengthen the robustness of results and conclusions obtained from analyses of datasets in basic and applied research.

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25. Why it is hard to find genes associated with social science traits: theoretical and empirical considerations.

Author

Chabris CF, Lee JJ, Benjamin DJ, Beauchamp JP, Glaeser EL, Borst G, Pinker S, and Laibson DI

Subjects
Adolescent, Adult, Behavior, Biological Phenomena, Female, Genetic Research, Genome-Wide Association Study, Humans, Male, Polymorphism, Single Nucleotide genetics, Selection, Genetic, Surveys and Questionnaires, Young Adult, Eye Color genetics, Genes, Hair Color genetics, Personality genetics, Social Sciences
Abstract

Objectives: We explain why traits of interest to behavioral scientists may have a genetic architecture featuring hundreds or thousands of loci with tiny individual effects rather than a few with large effects and why such an architecture makes it difficult to find robust associations between traits and genes., Methods: We conducted a genome-wide association study at 2 sites, Harvard University and Union College, measuring more than 100 physical and behavioral traits with a sample size typical of candidate gene studies. We evaluated predictions that alleles with large effect sizes would be rare and most traits of interest to social science are likely characterized by a lack of strong directional selection. We also carried out a theoretical analysis of the genetic architecture of traits based on R.A. Fisher's geometric model of natural selection and empirical analyses of the effects of selection bias and phenotype measurement stability on the results of genetic association studies., Results: Although we replicated several known genetic associations with physical traits, we found only 2 associations with behavioral traits that met the nominal genome-wide significance threshold, indicating that physical and behavioral traits are mainly affected by numerous genes with small effects., Conclusions: The challenge for social science genomics is the likelihood that genes are connected to behavioral variation by lengthy, nonlinear, interactive causal chains, and unraveling these chains requires allying with personal genomics to take advantage of the potential for large sample sizes as well as continuing with traditional epidemiological studies.

Published
2013
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