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26 results on '"Cornelius A Rietveld"'

1. Multivariate analysis reveals shared genetic architecture of brain morphology and human behavior

Author

Philip R. Jansen, Patrick J. F. Groenen, Cornelius A. Rietveld, Ronald de Vlaming, Alain Dagher, Philipp Koellinger, Eric A. W. Slob, de Vlaming, Ronald [0000-0001-6416-6067], Jansen, Philip R [0000-0003-1550-2444], Dagher, Alain [0000-0002-0945-5779], Groenen, Patrick JF [0000-0001-6683-8971], Rietveld, Cornelius A [0000-0003-4053-1861], Apollo - University of Cambridge Repository, Groenen, Patrick J F [0000-0001-6683-8971], Applied Economics, Child and Adolescent Psychiatry / Psychology, Econometrics, Erasmus School of Economics, Economics, Amsterdam Neuroscience - Complex Trait Genetics, Complex Trait Genetics, Jansen, Philip R. [0000-0003-1550-2444], Groenen, Patrick J. F. [0000-0001-6683-8971], Rietveld, Cornelius A. [0000-0003-4053-1861], Human genetics, APH - Aging & Later Life, and APH - Mental Health

Subjects
Male, Multivariate statistics, Multivariate analysis, Population genetics, Restricted maximum likelihood, QH301-705.5, 45/43, Medicine (miscellaneous), 631/208/1515, Biology, 631/208/457, Genetic correlation, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Humans, Biology (General), 030304 developmental biology, Cerebral Cortex, 0303 health sciences, Behavior, Models, Genetic, Genome, Human, Brain morphometry, article, Brain, Heritability, Phenotype, Genetic architecture, Evolutionary biology, Multivariate Analysis, Behavioural genetics, Female, General Agricultural and Biological Sciences, 030217 neurology & neurosurgery
Abstract

Human variation in brain morphology and behavior are related and highly heritable. Yet, it is largely unknown to what extent specific features of brain morphology and behavior are genetically related. Here, we introduce a computationally efficient approach for multivariate genomic-relatedness-based restricted maximum likelihood (MGREML) to estimate the genetic correlation between a large number of phenotypes simultaneously. Using individual-level data (N = 20,190) from the UK Biobank, we provide estimates of the heritability of gray-matter volume in 74 regions of interest (ROIs) in the brain and we map genetic correlations between these ROIs and health-relevant behavioral outcomes, including intelligence. We find four genetically distinct clusters in the brain that are aligned with standard anatomical subdivision in neuroscience. Behavioral traits have distinct genetic correlations with brain morphology which suggests trait-specific relevance of ROIs. These empirical results illustrate how MGREML can be used to estimate internally consistent and high-dimensional genetic correlation matrices in large datasets., Ronald de Vlaming and Eric Slob et al. present MGREML, a multivariate tool to estimate pairwise genetic correlations between multiple traits. They apply MGREML to UK Biobank data for 74 brain imaging phenotypes and 8 behavioral traits, demonstrating that these phenotypes have distinct genetic correlations with brain morphology.

Published
2021
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2. Genetic predispositions moderate the effectiveness of tobacco excise taxes

Author

Eric A. W. Slob, Cornelius A. Rietveld, Slob, Eric A. W. [0000-0002-1644-0735], Apollo - University of Cambridge Repository, Slob, Eric AW [0000-0002-1644-0735], and Applied Economics

Subjects
Databases, Factual, Single Nucleotide Polymorphisms, medicine.medical_treatment, Smoking Prevention, Smoking behavior, Habits, Tobacco Use, Smoking Habits, Psychology, Public and Occupational Health, Multidisciplinary, Tobacco control, Smoking, FOS: Social sciences, Genomics, Tobacco Products, Taxes, Medicine, Behavioral and Social Aspects of Health, Research Article, Nicotine, Tobacco Control, Political Science, Science, Public Policy, Tobacco Industry, Genetic Predisposition, Social sciences, SDG 3 - Good Health and Well-being, Environmental health, Tobacco, Genetics, Genome-Wide Association Studies, Genetic predisposition, medicine, Tobacco Smoking, Humans, Genetic Predisposition to Disease, Excise, Consumption (economics), Smoke, Medicine and health sciences, Behavior, Biology and life sciences, business.industry, Computational Biology, Human Genetics, Health and Retirement Study, Genome Analysis, United States, Genetics of Disease, Smoking cessation, Smoking Cessation, business
Abstract

Background Tobacco consumption is one of the leading causes of preventable death. In this study, we analyze whether someone’s genetic predisposition to smoking moderates the response to tobacco excise taxes. Methods We interact polygenic scores for smoking behavior with state-level tobacco excise taxes in longitudinal data (1992-2016) from the US Health and Retirement Study (N = 12,058). Results Someone’s genetic propensity to smoking moderates the effect of tobacco excise taxes on smoking behavior along the extensive margin (smoking vs. not smoking) and the intensive margin (the amount of tobacco consumed). In our analysis sample, we do not find a significant gene-environment interaction effect on smoking cessation. Conclusions When tobacco excise taxes are relatively high, those with a high genetic predisposition to smoking are less likely (i) to smoke, and (ii) to smoke heavily. While tobacco excise taxes have been effective in reducing smoking, the gene-environment interaction effects we observe in our sample suggest that policy makers could benefit from taking into account the moderating role of genes in the design of future tobacco control policies.

Published
2021

3. Effect of Genetic Propensity for Obesity on Income and Wealth Through Educational Attainment

Author

Pankaj C. Patel, Cornelius A. Rietveld, and Applied Economics

Subjects
Male, Longitudinal data, Endocrinology, Diabetes and Metabolism, Medicine (miscellaneous), 030209 endocrinology & metabolism, Body weight, Education, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, SDG 3 - Good Health and Well-being, Risk Factors, medicine, Genetic predisposition, Humans, Genetic Predisposition to Disease, 030212 general & internal medicine, Longitudinal Studies, Obesity, Genetic risk, 10. No inequality, Brief Cutting Edge Report, Aged, Nutrition and Dietetics, Epidemiology/Genetics, Individual income, Health and Retirement Study, Middle Aged, medicine.disease, Educational attainment, Brief Cutting Edge Reports, Income, Female, Psychology, Demography
Abstract

textabstractObjective: This study contributes to the literature on the income and wealth consequences of obesity by exploiting recent discoveries about the genetic basis of BMI. Methods: The relation between a genetic risk score (GRS) for BMI, which reflects the genetic predisposition to have a higher body weight, and income and wealth was analyzed in a longitudinal data set comprising 5,962 individuals (22,490 individual-year observations) from the US Health and Retirement Study. Results: Empirical analyses showed that the GRS for BMI lowers individual income and household wealth through the channel of lower educational attainment. Sex-stratified analyses showed that this effect is particularly significant among females. Conclusions: This study provides support for the negative effects of the GRS for BMI on individual income and household wealth through lower education for females. For males, the effects are estimated to be smaller and insignificant. The larger effects for females compared with males may be due to greater labor market taste-based discrimination faced by females.

Published
2019

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
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5. ADHD and later-life labor market outcomes in the United States

Author

Cornelius A. Rietveld, Pankaj C. Patel, and Applied Economics

Subjects
Employment, Male, Multifactorial Inheritance, Labor market outcomes, media_common.quotation_subject, J01, Economics, Econometrics and Finance (miscellaneous), Educational attainment, 03 medical and health sciences, 0302 clinical medicine, Polygenic risk score, Disability benefits, mental disorders, ADHD, Humans, Longitudinal Studies, 030212 general & internal medicine, Endogeneity, media_common, Estimation, Original Paper, Health economics, 030503 health policy & services, Health Policy, I14, Middle Aged, United States, Social security, Attention Deficit Disorder with Hyperactivity, 8. Economic growth, Cohort, Unemployment, Educational Status, Female, Demographic economics, 0305 other medical science, Psychology
Abstract

This study analyzes the relation between attention-deficit hyperactivity disorder (ADHD) and later-life labor market outcomes in the United States and whether these relationships are mediated by educational attainment. To overcome endogeneity concerns in the estimation of these relationships, we exploit the polygenic risk score (PRS) for ADHD in a cohort where the diagnosis of and treatment for ADHD were generally not available. We find that an increase in the PRS for ADHD reduces the likelihood of employment, individual income, and household wealth. Moreover, it increases the likelihood of receiving social security disability benefits, unemployment or worker compensation, and other governmental transfers. We provide evidence that educational attainment mediates these relationships to a considerable extent (14-58%).

Published
2019
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6. Genome-wide association meta-analysis of 78,308 individuals identifies new loci and genes influencing human intelligence

Author

Gerome Breen, Suzanne Sniekers, Neil Pendleton, Robert Plomin, Antony Payton, Magnus Johannesson, Anke R. Hammerschlag, Sven Stringer, Philipp Koellinger, Matt McGue, David Cesarini, Najaf Amin, Christopher F. Chabris, Delilah Zabaneh, Cornelia M. van Duijn, Cornelius A. Rietveld, Aysu Okbay, Jonathan R. I. Coleman, Michael B. Miller, Danielle Posthuma, Eva Krapohl, Erdogan Taskesen, William G. Iacono, Kyoko Watanabe, Philip R. Jansen, Patrik K. E. Magnusson, William E R Ollier, James J. Lee, Henning Tiemeier, M. Arfan Ikram, Neurology, Human genetics, Amsterdam Reproduction & Development (AR&D), Amsterdam Neuroscience - Complex Trait Genetics, Child and Adolescent Psychiatry / Psychology, Applied Economics, Epidemiology, Psychiatry, Mathematics, Complex Trait Genetics, Tinbergen Institute, Graduate School, and Human Genetics

Subjects
0301 basic medicine, Adult, Male, Linkage disequilibrium, Adolescent, European Continental Ancestry Group, Intelligence, Single-nucleotide polymorphism, Genome-wide association study, Nerve Tissue Proteins, Biology, Genetic correlation, Polymorphism, Single Nucleotide, Article, White People, Linkage Disequilibrium, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Genetics, Journal Article, Brain/metabolism, Nerve Tissue Proteins/genetics, Humans, Polymorphism, Child, Preschool, Gene, Aged, Human intelligence, Research, Intelligence/genetics, Brain, Infant, Single Nucleotide, Heritability, Middle Aged, Genetic architecture, 030104 developmental biology, Child, Preschool, Female, 030217 neurology & neurosurgery, White People/genetics, Genome-Wide Association Study, Meta-Analysis
Abstract

Intelligence is associated with important economic and health-related life outcomes. Despite intelligence having substantial heritability (0.54) and a confirmed polygenic nature, initial genetic studies were mostly underpowered. Here we report a meta- A nalysis for intelligence of 78,308 individuals. We identify 336 associated SNPs (METAL P < 5 × 10-8) in 18 genomic loci, of which 15 are new. Around half of the SNPs are located inside a gene, implicating 22 genes, of which 11 are new findings. Gene-based analyses identified an additional 30 genes (MAGMA P < 2.73 × 10-6), of which all but one had not been implicated previously. We show that the identified genes are predominantly expressed in brain tissue, and pathway analysis indicates the involvement of genes regulating cell development (MAGMA competitive P = 3.5 × 10-6). Despite the well-known difference in twin-based heritability for intelligence in childhood (0.45) and adulthood (0.80), we show substantial genetic correlation (rg = 0.89, LD score regression P = 5.4 × 10-29). These findings provide new insight into the genetic architecture of intelligence.

Published
2017
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7. Associations of autozygosity with a broad range of human phenotypes

Author

Dennis O. Mook-Kanamori, Salma M. Wakil, Lisa R. Yanek, Dominique P.V. de Kleijn, Gert J. de Borst, Alison D. Murray, Kamran Guity, Vincent W. V. Jaddoe, Mario Pirastu, Carole Ober, Giuseppe Matullo, Charles N. Rotimi, Daniela Ruggiero, Teresa Tusié-Luna, Wolfgang Lieb, Chew-Kiat Heng, John R. B. Perry, Hortensia Moreno-Macías, Jie Zhou, John M. Starr, Juhani Junttila, Lei Yu, Danielle Posthuma, Marcus Dörr, Yingchang Lu, Jonathan P. Bradfield, Einat Granot-Hershkovitz, Karina Meidtner, Wouter van Rheenen, T Esko, Maris Alver, Wen-Jane Lee, Zhengming Chen, Jennifer A. Brody, Paolo Gasparini, Yii-Der Ida Chen, Cinzia Sala, Peter P. Pramstaller, Gauri Prasad, Nana Matoba, Natalie Terzikhan, Simonetta Guarrera, Bjarke Feenstra, Peter Vollenweider, Smeeta Shrestha, Yi-Jen Hung, Lilja Stefansdottir, David R. Weir, Felix R. Day, Antonietta Robino, Liang Zhang, Lluis Quintana-Murci, Nicholas J. Timpson, Robyn E Wootton, Xue W. Mei, Dharambir K. Sanghera, Gisli Masson, Debbie A Lawlor, Thomas Meitinger, Sharon L.R. Kardia, Peter K. Joshi, Frank J. A. van Rooij, Claude Bouchard, Cassandra N. Spracklen, Ken K. Ong, Taulant Muka, Guanjie Chen, Laura J. Scott, Walter Palmas, Daniel I. Chasman, Sarah E. Medland, Krista Fischer, Blair H. Smith, Jon K. Sigurdsson, Leon Straker, Clara Viberti, Yuan Shi, Louis Pérusse, Peter J. van der Most, Timo Tõnis Sikka, Chris Haley, Kuang Lin, Leif Groop, Hester M. den Ruijter, Hakon Hakonarson, Masato Akiyama, Stephan J. L. Bakker, Sonja I. Berndt, Jeffery R. O'Connell, Cisca Wijmenga, Daniele Cusi, Lorena Orozco, Kristjan H. S. Moore, Kevin Sandow, Stephen S. Rich, Stephanie J. Loomis, George Davey Smith, Cornelia M. van Duijn, Sharvari Rahul Shukla, Agnar Helgason, Thorsten Kessler, Anuj Goel, Dan Mason, David W. Clark, James S. Pankow, Simona Vaccargiu, Uwe Völker, Tamara B. Harris, Matthew A. Allison, Clicerio Gonzalez, Sarju Ralhan, I-Te Lee, Matthias Laudes, Yen-Feng Chiu, Neil Poulter, Benjamin Lehne, John Wright, Lawrence F. Bielak, Philip L. De Jager, Reinhold Schmidt, Ya Xing Wang, Matthias Nauck, Diana L. Cousminer, Patrick Deelen, Ani Manichaikul, Stephen J. Chanock, Anders Hamsten, Barry I. Freedman, Gudmar Thorleifsson, Peter Kraft, Ozren Polasek, Jie Yao, Yoshinori Murakami, Paul M. Ridker, Anubha Mahajan, Struan F.A. Grant, Claudia Schurmann, Bjarni Gunnarsson, Catriona L. K. Barnes, Jessica van Setten, Sandosh Padmanabhan, Alena Stančáková, Markus M. Lerch, Anuradha Jagadeesan, Franco Giulianini, Daniel F. Gudbjartsson, Dwaipayan Bharadwaj, Shengchao Alfred Li, Peter S. Sever, Trevor A. Mori, Albertine J. Oldehinkel, Koichi Matsuda, Xueling Sim, Evangelos Evangelou, André G. Uitterlinden, Pekka Jousilahti, Yukihide Momozawa, Ioanna Tzoulaki, Chao A. Hsiung, Ginevra Biino, Murielle Bochud, Hannele Mattsson, Ilja M. Nolte, Sarah H. Wild, Patricia B. Munroe, Jianjun Liu, Bruce M. Psaty, Giriraj R. Chandak, Masahiro Kanai, Tony R. Merriman, Teemu Palviainen, Rodney A. Lea, Janie Corley, Nicholas J. Wareham, Alan B. Zonderman, Makoto Hirata, Matthew J. Bixley, Caroline Hayward, Nora Franceschini, Kristel R van Eijk, Etienne Patin, Daniel Shriner, Niek Verweij, Xiuqing Guo, Fredrik Karpe, Ruth J. F. Loos, Tiinamaija Tuomi, Ashley van der Spek, Patricia A. Peyser, Jessica D. Faul, Christian Fuchsberger, David Cesarini, Alex S. F. Doney, Janine F. Felix, Cornelius A. Rietveld, Jagadish Vangipurapu, Tanguy Corre, Line Skotte, Rajkumar Dorajoo, Catherine Igartua, Meena Kumari, Nona Sotoodehnia, Leonard H. van den Berg, Najaf Amin, Dale R. Nyholt, Harry Campbell, Massimiliano Cocca, Scott D. Gordon, Patrik K. E. Magnusson, John C. Chambers, Traci M. Bartz, Mike A. Nalls, Tin Aung, Nduna Dzimiri, Colin N. A. Palmer, Rob M. van Dam, Johanna Kuusisto, Russell P. Tracy, Anna Damulina, Pierre-Emmanuel Morange, Sylvain Foisy, Jing Hua Zhao, Nicholas G. Martin, Ching-Yu Cheng, Mariaelisa Graff, Rashmi B. Prasad, Alice Stanton, David-Alexandre Trégouët, Yu Guo, Helen R. Warren, Lyn R. Griffiths, Weihua Meng, Annika Tillander, Christa Meisinger, Albert V. Smith, Mark I. McCarthy, Jingyun Yang, Marine Germain, Neil Small, Linda Broer, Vilmundur Gudnason, Gunnar K. Pálsson, Michele K. Evans, Alexander Teumer, Mark J. Caulfield, Giorgia Girotto, Thomas Lumley, Tinca J. C. Polderman, Wei Zhao, Carlos A. Aguilar-Salinas, Jari Lahti, Matthew L. Albert, Yechiel Friedlander, Veikko Salomaa, Iona Y Millwood, Jan H. Veldink, Archie Campbell, Andres Metspalu, Ulf Gyllensten, Grant W. Montgomery, Veronique Vitart, Jai Rup Singh, Saima Afaq, Alan R. Shuldiner, Miao-Li Chee, Adebowale Adeyemo, Jennifer A. Smith, David A. van Heel, Jaspal S. Kooner, Daniela Toniolo, Cristian Pattaro, Jerome I. Rotter, John Whitfield, Melissa C. Smart, Kari E. North, Salman M. Tajuddin, Tallapragada Divya Sri Priyanka, Christopher A. Haiman, Diane M. Becker, Bernhard K. Krämer, Paul Elliott, Lihua Wang, He Gao, Patrick Sulem, Jinyan Huang, Chiea Chuen Khor, Ruifang Li-Gao, Åsa Johansson, Winfried März, Shai Carmi, Ilaria Gandin, Eric Boerwinkle, Gardar Sveinbjornsson, Saskia P. Hagenaars, Sander W. van der Laan, Gerard Pasterkamp, E-Shyong Tai, Hagit Hochner, Yih Chung Tham, Kent D. Taylor, Kari Stefansson, Matt J. Neville, Craig E. Pennell, Yanchun Bao, Annelot M. Dekker, Helena Schmidt, Mehdi Hedayati, Joshua Elliott, Ian J. Deary, Iris E. Jansen, Judith B. Borja, Edith Hofer, Martin Gögele, Igor Rudan, Lude Franke, Matthias Munz, Folkert W. Asselbergs, Bengt Sennblad, Imo Hofer, John D. Rioux, Pim van der Harst, Bahareh Sedaghati-khayat, Giovanni Cugliari, Morris A. Swertz, Francine Grodstein, Erwin P. Bottinger, Carol A. Wang, Andre Franke, Brian F. Meyer, Adele M. Taylor, Klodian Dhana, Jian'an Luan, Constance Turman, Robert A. Scott, May E. Montasser, Alison Pattie, Marco Brumat, Liming Li, Heiner Boeing, Karen L. Mohlke, Clemens Baumbach, Bishwa Raj Sapkota, Unnur Thorsteinsdottir, Naveed Sattar, Amy R. Bentley, Matthias B. Schulze, Ivana Kolcic, Stella Trompet, Sarah E. Harris, Ayo P. Doumatey, Charumathi Sabanayagam, David Eccles, Mary F. Feitosa, Jost B. Jonas, Massimo Mezzavilla, Mark O. Goodarzi, David Ellinghaus, Heribert Schunkert, Christian Gieger, Heikki V. Huikuri, Lingyao Zeng, Johan G. Eriksson, Woon-Puay Koh, Yucheng Jia, Gurpreet Singh Wander, James F. Wilson, Torgny Karlsson, Steven C. Hunt, Weihua Zhang, Maria Pina Concas, Zoltán Kutalik, Rebecca Rohde, Chittaranjan S. Yajnik, Yasaman Saba, Dabeeru C. Rao, Robin G. Walters, Reedik Mägi, Marie Loh, Eero Vuoksimaa, Josyf C. Mychaleckyj, Katri Räikkönen, Philippe Goyette, M. Arfan Ikram, Alicia Huerta-Chagoya, David J. Porteous, Teresa Nutile, J. Wouter Jukema, Noha A. Yousri, Yoichiro Kamatani, Maryam S. Daneshpour, Babette S. Zemel, Rona J. Strawbridge, Tien Yin Wong, Claudia Langenberg, Amy Moore, Marcus E. Kleber, Fereidoun Azizi, Avner Halevy, Erika Salvi, Francis S. Collins, Markku Laakso, Tim Kacprowski, S. Sunna Ebenesersdóttir, William R. Scott, Michael Boehnke, Jin-Fang Chai, Markus Perola, Nicola Pirastu, Wayne Huey-Herng Sheu, Robert Karlsson, Lenore J. Launer, Lili Milani, Renée de Mutsert, Fernando Rivadeneira, David A. Bennett, Nicola D. Kerrison, Paolo Manunta, Graciela E. Delgado, Magnus Johannesson, Carolina Medina-Gomez, Alanna C. Morrison, Kay-Tee Khaw, Jian-Min Yuan, Jaakko Kaprio, Melanie Waldenberger, Ralf Ewert, Hugoline G. de Haan, Andrew A. Hicks, Yukinori Okada, Maria Sabater-Lleal, Marilyn C. Cornelis, Stephanie J. London, Federica Rizzi, Jeanette Erdmann, Marina Ciullo, Michiaki Kubo, University of Edinburgh, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Osaka University Graduate School of Medicine, Laboratory for Cardiovascular Genomics and Informatics [Yokohama] (RIKEN IMS), RIKEN Center for Integrative Medical Sciences [Yokohama] (RIKEN IMS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN)-RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), deCODE genetics [Reykjavik], Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK (BIHR), Area Science Park, Università degli studi di Trieste = University of Trieste, MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Interfaculty Institute for Genetics and Functional Genomics, Universität Greifswald - University of Greifswald, Harbor UCLA Medical Center [Torrance, Ca.], Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, Department of Electrical and Computer Engineering [Waterloo] (ECE), University of Waterloo [Waterloo], Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Institute of Pop. Genetics, CNR, Sassari, Shardna life science Pula Cagliari, Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne = University of Lausanne (UNIL), Medstar Research Institute, Florida State University [Tallahassee] (FSU), University Medical Center [Utrecht], Centre for Population Health Sciences, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), California State University [Sacramento], Department of Thrombosis and Haemostasis, Leiden University Medical Center (LUMC), Universiteit Leiden-Universiteit Leiden, Medical University Graz, Department of Neurology, Alzheimer Centre, VU Medical Centre, Amsterdam, Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty of Mannheim, University of Heidelberg, Heidelberg, Frederick National Laboratory for Cancer Research (FNLCR), Wellcome Trust Centre of Human Genetics, University of Oxford, Department of Epidemiology, German Institute of Human Nutrition, University Medical Center Groningen [Groningen] (UMCG), Institute of Genetics and Biophysics, National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR), Department of Medicine, Surgery, and Dentistry, University of Milano, Icelandic Heart Association, Kopavogur, Iceland., Department of Epidemiology [Rotterdam], Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Glasgow, Department of Cardiology, Leiden University Medical Center, Leiden, Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, Queen Mary University of London (QMUL), General Internal Medicine, Johns Hopkins School of Medicine, Johns Hopkins University School of Medicine [Baltimore], Institut de biologie moléculaire des plantes (IBMP), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Immunobiologie des Cellules dendritiques, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Translationnelle - Center for Translational Science (CRT), Institut Pasteur [Paris] (IP), Genentech, Inc., Genentech, Inc. [San Francisco], University of Tartu, Duke-NUS Medical School [Singapore], Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke (DifE), Leibniz Association, Human Genome Sequencing Center, Baylor College of Medicine, Baylor College of Medicine (BCM), Baylor University-Baylor University, University of San Carlos, Office of Population Studies Foundation, Icahn School of Medicine at Mount Sinai [New York] (MSSM), King‘s College London, Division of Cancer Epidemiology and Genetics, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), University of Oxford, Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty of Mannheim, University of Heidelberg, Division of Molecular & Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, Department of Internal Medicine B, University Medicine Greifswald, Greifswald, University of Chicago, University of Huddersfield, Infectious diseases division, Department of internal medicine, Washington University in Saint Louis (WUSTL), Section on Nephrology [Winston-Salem, NC, USA] (Department of Internal Medicine), Wake Forest School of Medicine [Winston-Salem], Wake Forest Baptist Medical Center-Wake Forest Baptist Medical Center, Radcliffe Department of Medicine [Oxford], Harvard School of Public Health, Kunming University of Science and Technology (KMUST), Sans affiliation, University of Southern California (USC), National Institute on Aging [Bethesda, USA] (NIA), National Institutes of Health [Bethesda] (NIH), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), MRC Centrer for Nutritional Epidemiology and Cancer Prevention and Survival, University of Cambridge [UK] (CAM), National University of Singapore (NUS), Experimental Cardiology Laboratory (ECL), Unirversity Medical Center, Department of Medical Statistics, Epidemiology and Medical Informatics, University of Zagreb, Department of Medical Genetics, Department of Medicine, University of Eastern Finland-Kuopio University Hospital, MRC Epidemiology Unit, University of Cambridge [UK] (CAM)-Institute of Metabolic Science, Capital Normal University [Beijing], Saw Swee Hock School of Public Health, National Institute for Environmental Health Sciences Research Triangle Park, Brown University, MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, Toyota Research Institute, Helmholtz Zentrum München = German Research Center for Environmental Health, Department of Chemistry and Biochemistry [Boulder], University of Colorado [Boulder], Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital de la Timone [CHU - APHM] (TIMONE), Metacohorts Consortium, Universiteit Leiden, Institute of Clinical Chemistry and Laboratory Medicine, University of Groningen [Groningen], Medical Research Concil Epidemiology Unit, Institute of Medical Science, Faculty of Medicine, Genetics and Pathology, Imperial College London, Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Brigham and Women's Hospital [Boston], Erasmus University Rotterdam, Department of Chronic Disease Prevention, National Institute for Health and Welfare [Helsinki], Department of Biostatistics and Center for Statistical Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU), Stockholm Bioinformatics Center (SBC), Stockholm University, Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, University of Utrecht, Utrecht, INRH, Department of Genetics, Los Angeles Biomedical Research Institute (LA BioMed), Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán - National Institute of Medical Science and Nutrition Salvador Zubiran [Mexico], Western General Hospital, German Research Center for Environmental Health - Helmholtz Center München (GmbH), Medical Research Council, Division of Cancer Control and Population Sciences, University of Pittsburgh Cancer Institute-University of Pittsburgh Graduate School of Public Health, Zhengzhou University of Light Industry, Department of Electrical and Electronic Engineering [Niigata Univ.], Niigata University, Genetic Epidemiology Unit, University College of London [London] (UCL), Aston Business School, Aston University [Birmingham], Division of Cancer Epidemiology and Genetics [Bethesda, MD, États-Unis], Centre Hospitalier Universitaire Vaudois (CHUV), Pennington Biomedical Research Center, University of Washington [Seattle], Guy's and St Thomas' Hospitals, Northwestern Polytechnical University [Xi'an] (NPU), Department of Social Medicine, University of Bristol [Bristol], Department of Genomics of Common Disease [London, UK], Imperial College London-Hammersmith Hospital NHS Imperial College Healthcare, Department of Internal Medicine, Institute of Clinical Molecular Biology, Kiel University, Medizinische Klinik II, Universität zu Lübeck = University of Lübeck [Lübeck], Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of Ioannina, Institute for Social Research, University of Michigan System-University of Michigan System, Division of Statistical Genomics, Washington University School of Medicine, Institute for Clinical Molecular Biology, Christian-Albrechts-Universität zu Kiel (CAU), Department of Physics, RISSC-Lab-University of Naples Federico II = Università degli studi di Napoli Federico II, Lund University [Lund], Icelandic Heart Association, Heart Preventive Clinic and Research Institute, The Center for Applied Genomics, Children’s Hospital of Philadelphia (CHOP ), Génétique moléculaire de la neurotransmission et des processus neurodégénératifs (LGMNPN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Medical Research Center Oulu, University of Oulu, University of Utah School of Medicine [Salt Lake City], The Generation R Study, Pediatrics, Epidemiology, Center for Translational and Computational Neuroimmunology [New York, NY, États-Unis] (CTCN), Department of Neurology [New York, NY, États-Unis], Columbia University Medical Center (CUMC), Columbia University [New York]-Columbia University [New York]-Columbia University Medical Center (CUMC), Columbia University [New York]-Columbia University [New York], Universität Heidelberg [Heidelberg] = Heidelberg University, Interuniversity Cardiology Institute Netherlands, School of Public Health, University of Michigan [Dearborn], Department of Epidemiology and Public Health, University of Kuopio, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Institute of Epidemiology and Biobank PopGen, Department of Biostatistics, University of Washington, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Clinical Institute of Medical and Chemical Laboratory Diagnostics, Karl-Franzens-Universität Graz, Department of Genetics, Biology and Biochemistry, Università degli studi di Torino = University of Turin (UNITO), Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), QIMR Berghofer Medical Research Institute, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC)-UNC Gillings School of Global Public Health-Carolina Center for Genome Sciences, University of Illinois [Chicago] (UIC), University of Illinois System, Experimental Cardiology Laboratory, Genetic Epidemiology and Clinical Research Group, Umea University Hospital, Functional Genomics, Erasmus Medical Centre, National Human Genome Research Institute (NHGRI), School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), Department of Pathological Biochemistry, Royal Infirmary, German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Institute of Metabolic Science, MRC, University of Maryland School of Medicine [Baltimore, MD, USA], Centre for Molecular Epidemiology, Centre for Causal Analyses in Translational Epidemiology, University of Bristol [Bristol]-Medical Research Council, IRCCS San Raffaele Scientific Institute [Milan, Italie], U937, Génomique cardiovasculaire, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), University of Michigan System, HMNC Brain Health, Singapore Eye Research Institute, Partenaires INRAE, Institut d'Électronique et des Technologies du numéRique (IETR), Université de Nantes (UN)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Institute for Molecular Medicine Finland [Helsinki] (FIMM), Helsinki Institute of Life Science (HiLIFE), Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Department of Psychiatry and Psychotherapy, Rheinische Friedrich-Wilhelms-Universität Bonn, University of Groningen, Department of Genomics of Common Disease, Department of Microbiology, The Freeman Hospital, Department Biostatistics University of North Carolina, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, Clark, D. W., Okada, Y., Moore, K. H. S., Mason, D., Pirastu, N., Gandin, I., Mattsson, H., Barnes, C. L. K., Lin, K., Zhao, J. H., Deelen, P., Rohde, R., Schurmann, C., Guo, X., Giulianini, F., Zhang, W., Medina-Gomez, C., Karlsson, R., Bao, Y., Bartz, T. M., Baumbach, C., Biino, G., Bixley, M. J., Brumat, M., Chai, J. -F., Corre, T., Cousminer, D. L., Dekker, A. M., Eccles, D. A., van Eijk, K. R., Fuchsberger, C., Gao, H., Germain, M., Gordon, S. D., de Haan, H. G., Harris, S. E., Hofer, E., Huerta-Chagoya, A., Igartua, C., Jansen, I. E., Jia, Y., Kacprowski, T., Karlsson, T., Kleber, M. E., Li, S. A., Li-Gao, R., Mahajan, A., Matsuda, K., Meidtner, K., Meng, W., Montasser, M. E., van der Most, P. J., Munz, M., Nutile, T., Palviainen, T., Prasad, G., Prasad, R. B., Priyanka, T. D. S., Rizzi, F., Salvi, E., Sapkota, B. R., Shriner, D., Skotte, L., Smart, M. C., Smith, A. V., van der Spek, A., Spracklen, C. N., Strawbridge, R. J., Tajuddin, S. M., Trompet, S., Turman, C., Verweij, N., Viberti, C., Wang, L., Warren, H. R., Wootton, R. E., Yanek, L. R., Yao, J., Yousri, N. A., Zhao, W., Adeyemo, A. A., Afaq, S., Aguilar-Salinas, C. A., Akiyama, M., Albert, M. L., Allison, M. A., Alver, M., Aung, T., Azizi, F., Bentley, A. R., Boeing, H., Boerwinkle, E., Borja, J. B., de Borst, G. J., Bottinger, E. P., Broer, L., Campbell, H., Chanock, S., Chee, M. -L., Chen, G., Chen, Y. -D. I., Chen, Z., Chiu, Y. -F., Cocca, M., Collins, F. S., Concas, M. P., Corley, J., Cugliari, G., van Dam, R. M., Damulina, A., Daneshpour, M. S., Day, F. R., Delgado, G. E., Dhana, K., Doney, A. S. F., Dorr, M., Doumatey, A. P., Dzimiri, N., Ebenesersdottir, S. S., Elliott, J., Elliott, P., Ewert, R., Felix, J. F., Fischer, K., Freedman, B. I., Girotto, G., Goel, A., Gogele, M., Goodarzi, M. O., Graff, M., Granot-Hershkovitz, E., Grodstein, F., Guarrera, S., Gudbjartsson, D. F., Guity, K., Gunnarsson, B., Guo, Y., Hagenaars, S. P., Haiman, C. A., Halevy, A., Harris, T. B., Hedayati, M., van Heel, D. A., Hirata, M., Hofer, I., Hsiung, C. A., Huang, J., Hung, Y. -J., Ikram, M. A., Jagadeesan, A., Jousilahti, P., Kamatani, Y., Kanai, M., Kerrison, N. D., Kessler, T., Khaw, K. -T., Khor, C. C., de Kleijn, D. P. V., Koh, W. -P., Kolcic, I., Kraft, P., Kramer, B. K., Kutalik, Z., Kuusisto, J., Langenberg, C., Launer, L. J., Lawlor, D. A., Lee, I. -T., Lee, W. -J., Lerch, M. M., Li, L., Liu, J., Loh, M., London, S. J., Loomis, S., Lu, Y., Luan, J., Magi, R., Manichaikul, A. W., Manunta, P., Masson, G., Matoba, N., Mei, X. W., Meisinger, C., Meitinger, T., Mezzavilla, M., Milani, L., Millwood, I. Y., Momozawa, Y., Moore, A., Morange, P. -E., Moreno-Macias, H., Mori, T. A., Morrison, A. C., Muka, T., Murakami, Y., Murray, A. D., de Mutsert, R., Mychaleckyj, J. C., Nalls, M. A., Nauck, M., Neville, M. J., Nolte, I. M., Ong, K. K., Orozco, L., Padmanabhan, S., Palsson, G., Pankow, J. S., Pattaro, C., Pattie, A., Polasek, O., Poulter, N., Pramstaller, P. P., Quintana-Murci, L., Raikkonen, K., Ralhan, S., Rao, D. C., van Rheenen, W., Rich, S. S., Ridker, P. M., Rietveld, C. A., Robino, A., van Rooij, F. J. A., Ruggiero, D., Saba, Y., Sabanayagam, C., Sabater-Lleal, M., Sala, C. F., Salomaa, V., Sandow, K., Schmidt, H., Scott, L. J., Scott, W. R., Sedaghati-Khayat, B., Sennblad, B., van Setten, J., Sever, P. J., Sheu, W. H. -H., Shi, Y., Shrestha, S., Shukla, S. R., Sigurdsson, J. K., Sikka, T. T., Singh, J. R., Smith, B. H., Stancakova, A., Stanton, A., Starr, J. M., Stefansdottir, L., Straker, L., Sulem, P., Sveinbjornsson, G., Swertz, M. A., Taylor, A. M., Taylor, K. D., Terzikhan, N., Tham, Y. -C., Thorleifsson, G., Thorsteinsdottir, U., Tillander, A., Tracy, R. P., Tusie-Luna, T., Tzoulaki, I., Vaccargiu, S., Vangipurapu, J., Veldink, J. H., Vitart, V., Volker, U., Vuoksimaa, E., Wakil, S. M., Waldenberger, M., Wander, G. S., Wang, Y. X., Wareham, N. J., Wild, S., Yajnik, C. S., Yuan, J. -M., Zeng, L., Zhang, L., Zhou, J., Amin, N., Asselbergs, F. W., Bakker, S. J. L., Becker, D. M., Lehne, B., Bennett, D. A., van den Berg, L. H., Berndt, S. I., Bharadwaj, D., Bielak, L. F., Bochud, M., Boehnke, M., Bouchard, C., Bradfield, J. P., Brody, J. A., Campbell, A., Carmi, S., Caulfield, M. J., Cesarini, D., Chambers, J. C., Chandak, G. R., Cheng, C. -Y., Ciullo, M., Cornelis, M., Cusi, D., Smith, G. D., Deary, I. J., Dorajoo, R., van Duijn, C. M., Ellinghaus, D., Erdmann, J., Eriksson, J. G., Evangelou, E., Evans, M. K., Faul, J. D., Feenstra, B., Feitosa, M., Foisy, S., Franke, A., Friedlander, Y., Gasparini, P., Gieger, C., Gonzalez, C., Goyette, P., Grant, S. F. A., Griffiths, L. R., Groop, L., Gudnason, V., Gyllensten, U., Hakonarson, H., Hamsten, A., van der Harst, P., Heng, C. -K., Hicks, A. A., Hochner, H., Huikuri, H., Hunt, S. C., Jaddoe, V. W. V., De Jager, P. L., Johannesson, M., Johansson, A., Jonas, J. B., Jukema, J. W., Junttila, J., Kaprio, J., Kardia, S. L. R., Karpe, F., Kumari, M., Laakso, M., van der Laan, S. W., Lahti, J., Laudes, M., Lea, R. A., Lieb, W., Lumley, T., Martin, N. G., Marz, W., Matullo, G., Mccarthy, M. I., Medland, S. E., Merriman, T. R., Metspalu, A., Meyer, B. F., Mohlke, K. L., Montgomery, G. W., Mook-Kanamori, D., Munroe, P. B., North, K. E., Nyholt, D. R., O'Connell, J. R., Ober, C., Oldehinkel, A. J., Palmas, W., Palmer, C., Pasterkamp, G. G., Patin, E., Pennell, C. E., Perusse, L., Peyser, P. A., Pirastu, M., Polderman, T. J. C., Porteous, D. J., Posthuma, D., Psaty, B. M., Rioux, J. D., Rivadeneira, F., Rotimi, C., Rotter, J. I., Rudan, I., Den Ruijter, H. M., Sanghera, D. K., Sattar, N., Schmidt, R., Schulze, M. B., Schunkert, H., Scott, R. A., Shuldiner, A. R., Sim, X., Small, N., Smith, J. A., Sotoodehnia, N., Tai, E. -S., Teumer, A., Timpson, N. J., Toniolo, D., Tregouet, D. -A., Tuomi, T., Vollenweider, P., Wang, C. A., Weir, D. R., Whitfield, J. B., Wijmenga, C., Wong, T. -Y., Wright, J., Yang, J., Yu, L., Zemel, B. S., Zonderman, A. B., Perola, M., Magnusson, P. K. E., Uitterlinden, A. G., Kooner, J. S., Chasman, D. I., Loos, R. J. F., Franceschini, N., Franke, L., Haley, C. S., Hayward, C., Walters, R. G., Perry, J. R. B., Esko, T., Helgason, A., Stefansson, K., Joshi, P. K., Kubo, M., Wilson, J. F., Læknadeild (HÍ), Faculty of Medicine (UI), Félagsfræði-, mannfræði- og þjóðfræðideild (HÍ), Faculty of Sociology, Anthropology and Folkloristics (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), School of Engineering and Natural Sciences (UI), Verkfræði- og náttúruvísindasvið (HÍ), Félagsvísindasvið (HÍ), School of Social Sciences (UI), Háskóli Íslands, University of Iceland, Clark, David W [0000-0002-1025-9185], Okada, Yukinori [0000-0002-0311-8472], Moore, Kristjan H S [0000-0002-9579-4362], Mason, Dan [0000-0002-0026-9216], Pirastu, Nicola [0000-0002-5363-3886], Gandin, Ilaria [0000-0003-3196-2491], Deelen, Patrick [0000-0002-5654-3966], Schurmann, Claudia [0000-0003-4158-9192], Medina-Gomez, Carolina [0000-0001-7999-5538], Karlsson, Robert [0000-0002-8949-2587], Bao, Yanchun [0000-0002-6102-5098], Biino, Ginevra [0000-0002-9936-946X], Brumat, Marco [0000-0003-3268-039X], Chai, Jin-Fang [0000-0003-3770-1137], Eccles, David A [0000-0003-4634-4995], Gordon, Scott D [0000-0001-7623-328X], Harris, Sarah E [0000-0002-4941-5106], Kacprowski, Tim [0000-0002-5393-2413], Karlsson, Torgny [0000-0001-8095-6149], Kleber, Marcus E [0000-0003-0663-7275], Mahajan, Anubha [0000-0001-5585-3420], Matsuda, Koichi [0000-0001-7292-2686], Meng, Weihua [0000-0001-5388-8494], van der Most, Peter J [0000-0001-8450-3518], Munz, Matthias [0000-0002-4728-3357], Palviainen, Teemu [0000-0002-7847-8384], Prasad, Rashmi B [0000-0002-4400-6741], Salvi, Erika [0000-0002-2724-2291], Skotte, Line [0000-0002-7398-1271], van der Spek, Ashley [0000-0001-7136-0159], Spracklen, Cassandra N [0000-0003-3590-7182], Strawbridge, Rona J [0000-0001-8506-3585], Tajuddin, Salman M [0000-0002-7919-8528], Verweij, Niek [0000-0002-4303-7685], Yanek, Lisa R [0000-0001-7117-1075], Zhao, Wei [0000-0001-7388-0692], Albert, Matthew L [0000-0001-7285-6973], Bentley, Amy R [0000-0002-0827-9101], Chanock, Stephen [0000-0002-2324-3393], Chen, Zhengming [0000-0001-6423-105X], Chiu, Yen-Feng [0000-0002-3352-4500], Cocca, Massimiliano [0000-0002-1127-7596], Collins, Francis S [0000-0002-1023-7410], Cugliari, Giovanni [0000-0002-6080-0718], Damulina, Anna [0000-0001-8241-2727], Day, Felix R [0000-0003-3789-7651], Dhana, Klodian [0000-0002-6397-7009], Dzimiri, Nduna [0000-0003-3395-5754], Elliott, Paul [0000-0002-7511-5684], Felix, Janine F [0000-0002-9801-5774], Freedman, Barry I [0000-0003-0275-5530], Girotto, Giorgia [0000-0003-4507-6589], Goel, Anuj [0000-0003-2307-4021], Goodarzi, Mark O [0000-0001-6364-5103], Gudbjartsson, Daniel F [0000-0002-5222-9857], Guity, Kamran [0000-0002-8379-9668], van Heel, David A [0000-0002-0637-2265], Hirata, Makoto [0000-0002-9994-9958], Ikram, M Arfan [0000-0003-0372-8585], Kamatani, Yoichiro [0000-0001-8748-5597], Kanai, Masahiro [0000-0001-5165-4408], Khor, Chiea Chuen [0000-0002-1128-4729], Kolcic, Ivana [0000-0001-7918-6052], Langenberg, Claudia [0000-0002-5017-7344], Lawlor, Deborah A [0000-0002-6793-2262], Liu, Jianjun [0000-0002-3255-3019], London, Stephanie J [0000-0003-4911-5290], Luan, Jian’an [0000-0003-3137-6337], Matoba, Nana [0000-0001-5329-0134], Mei, Xue W [0000-0002-6279-4884], Mezzavilla, Massimo [0000-0002-9000-4595], Milani, Lili [0000-0002-5323-3102], Mori, Trevor A [0000-0002-5264-9229], Murakami, Yoshinori [0000-0002-2826-4396], Murray, Alison D [0000-0003-4915-4847], Mychaleckyj, Josyf C [0000-0003-2595-0005], Neville, Matt J [0000-0002-6004-5433], Nolte, Ilja M [0000-0001-5047-4077], Ong, Ken K [0000-0003-4689-7530], Pálsson, Gunnar [0000-0002-8231-3961], Pankow, James S [0000-0001-7076-483X], Pattaro, Cristian [0000-0002-4119-0109], Quintana-Murci, Lluis [0000-0003-2429-6320], van Rheenen, Wouter [0000-0002-5860-1533], Rich, Stephen S [0000-0003-3872-7793], Rietveld, Cornelius A [0000-0003-4053-1861], Ruggiero, Daniela [0000-0003-3898-7827], Sabanayagam, Charumathi [0000-0002-4042-4719], Sabater-Lleal, Maria [0000-0002-0128-379X], Sala, Cinzia Felicita [0000-0003-2514-2075], Salomaa, Veikko [0000-0001-7563-5324], Scott, Laura J [0000-0002-4886-5084], Sedaghati-Khayat, Bahareh [0000-0002-7665-8648], Sennblad, Bengt [0000-0002-4360-8003], van Setten, Jessica [0000-0002-4934-7510], Smith, Blair H [0000-0002-5362-9430], Stančáková, Alena [0000-0002-1375-0252], Stanton, Alice [0000-0002-4961-165X], Straker, Leon [0000-0002-7786-4128], Sulem, Patrick [0000-0001-7123-6123], Swertz, Morris A [0000-0002-0979-3401], Taylor, Kent D [0000-0002-2756-4370], Tzoulaki, Ioanna [0000-0002-4275-9328], Veldink, Jan H [0000-0001-5572-9657], Vitart, Veronique [0000-0002-4991-3797], Völker, Uwe [0000-0002-5689-3448], Wander, Gurpreet S [0000-0002-4596-4247], Wang, Ya Xing [0000-0003-2749-7793], Wild, Sarah [0000-0001-7824-2569], Yuan, Jian-Min [0000-0002-4620-3108], Asselbergs, Folkert W [0000-0002-1692-8669], Boehnke, Mike [0000-0002-6442-7754], Bouchard, Claude [0000-0002-0048-491X], Brody, Jennifer A [0000-0001-8509-148X], Campbell, Archie [0000-0003-0198-5078], Caulfield, Mark J [0000-0001-9295-3594], Smith, George Davey [0000-0002-1407-8314], Dorajoo, Rajkumar [0000-0001-6608-2051], Ellinghaus, David [0000-0002-4332-6110], Erdmann, Jeanette [0000-0002-4486-6231], Evangelou, Evangelos [0000-0002-5488-2999], Feenstra, Bjarke [0000-0003-1478-649X], Feitosa, Mary [0000-0002-0933-2410], Franke, Andre [0000-0003-1530-5811], Grant, Struan F A [0000-0003-2025-5302], Griffiths, Lyn R [0000-0002-6774-5475], Groop, Leif [0000-0002-0187-3263], Gudnason, Vilmundur [0000-0001-5696-0084], van der Harst, Pim [0000-0002-2713-686X], Heng, Chew-Kiat [0000-0002-7309-9473], Hicks, Andrew A [0000-0001-6320-0411], Jaddoe, Vincent W V [0000-0003-2939-0041], De Jager, Philip L [0000-0002-8057-2505], Johannesson, Magnus [0000-0001-8759-6393], Johansson, Åsa [0000-0002-2915-4498], Jonas, Jost B [0000-0003-2972-5227], Jukema, J Wouter [0000-0002-3246-8359], Kaprio, Jaakko [0000-0002-3716-2455], Laakso, Markku [0000-0002-3394-7749], van der Laan, Sander W [0000-0001-6888-1404], Lahti, Jari [0000-0002-4310-5297], Martin, Nicholas G [0000-0003-4069-8020], Medland, Sarah E [0000-0003-1382-380X], Merriman, Tony R [0000-0003-0844-8726], Metspalu, Andres [0000-0002-3718-796X], Mohlke, Karen L [0000-0001-6721-153X], Montgomery, Grant W [0000-0002-4140-8139], Munroe, Patricia B [0000-0002-4176-2947], Nyholt, Dale R [0000-0001-7159-3040], Ober, Carole [0000-0003-4626-9809], Oldehinkel, Albertine J [0000-0003-3925-3913], Palmer, Colin [0000-0002-6415-6560], Perusse, Louis [0000-0001-6440-9698], Polderman, Tinca J. C. [0000-0001-5564-301X], Porteous, David J [0000-0003-1249-6106], Rioux, John D [0000-0001-7560-8326], Rivadeneira, Fernando [0000-0001-9435-9441], Rotimi, Charles [0000-0001-5759-053X], Rotter, Jerome I [0000-0001-7191-1723], Rudan, Igor [0000-0001-6993-6884], Sattar, Naveed [0000-0002-1604-2593], Sim, Xueling [0000-0002-1233-7642], Smith, Jennifer A [0000-0002-3575-5468], Teumer, Alexander [0000-0002-8309-094X], Timpson, Nicholas J [0000-0002-7141-9189], Tuomi, Tiinamaija [0000-0002-8306-6202], Wang, Carol A [0000-0002-4301-3974], Weir, David R [0000-0002-1661-2402], Whitfield, John B [0000-0002-1103-0876], Magnusson, Patrik K. E. [0000-0002-7315-7899], Uitterlinden, André G [0000-0002-7276-3387], Loos, Ruth J. F. [0000-0002-8532-5087], Franke, Lude [0000-0002-5159-8802], Haley, Chris S [0000-0002-9811-0210], Hayward, Caroline [0000-0002-9405-9550], Walters, Robin G [0000-0002-9179-0321], Joshi, Peter K [0000-0002-6361-5059], Wilson, James F [0000-0001-5751-9178], Apollo - University of Cambridge Repository, Moore, Kristjan HS [0000-0002-9579-4362], Luan, Jian'an [0000-0003-3137-6337], Grant, Struan FA [0000-0003-2025-5302], Jaddoe, Vincent WV [0000-0003-2939-0041], Polderman, Tinca JC [0000-0001-5564-301X], Magnusson, Patrik KE [0000-0002-7315-7899], Loos, Ruth JF [0000-0002-8532-5087], Neurology, Human genetics, Amsterdam Reproduction & Development (AR&D), Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Cardiovascular Centre (CVC), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Stem Cell Aging Leukemia and Lymphoma (SALL), Institute for Molecular Medicine Finland, Department of Psychology and Logopedics, University Management, Developmental Psychology Research Group, Staff Services, Cognitive and Brain Aging, Research Programs Unit, Diabetes and Obesity Research Program, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, Clinicum, University of Helsinki, Centre of Excellence in Complex Disease Genetics, Department of Public Health, Genetic Epidemiology, Helsinki Collegium for Advanced Studies, HUS Abdominal Center, Endokrinologian yksikkö, Bradford Teaching Hospitals NHS Foundation Trust [Bradford, UK] (BTHFT), University of Trieste, Université de Lausanne (UNIL), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Consiglio Nazionale delle Ricerche (CNR), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Institut Pasteur [Paris], University of Oxford [Oxford], Medical Genetics, Dept. RSD and Public Health, IRCCS-Burlo Garofolo/University of Trieste, sans affiliation, Helmholtz-Zentrum München (HZM), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institute of Cardiovascular Science, University College London, Hammersmith Hospital NHS Imperial College Healthcare-Imperial College London, Universität zu Lübeck [Lübeck], University of Ioannina Medical School, Università degli studi di Napoli Federico II-RISSC-Lab, Universität Heidelberg [Heidelberg], University of Turin, University of California-University of California, Nantes Université (NU)-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)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), University of Helsinki-University of Helsinki, Université de Nantes (UN)-Université de Rennes 1 (UR1), Erasmus MC other, Internal Medicine, and Applied Economics

Subjects
0301 basic medicine, 631/208/1397, Chemistry(all), Health Status, [SDV]Life Sciences [q-bio], LOCI, General Physics and Astronomy, MESH: Haplotype, MESH: Cognition, 030105 genetics & heredity, Runs of Homozygosity, Biochemistry, Consanguinity, Cognition, Inbreeding depression, 2.1 Biological and endogenous factors, Body Size, Inbreeding, Skyldleikarækt, Aetiology, Human phenotypes, lcsh:Science, MESH: Health Status, Genetics, Multidisciplinary, Inbreeding Depression, Confounding, Homozygote, RUNS, 631/208/205, 631/208/721, 3. Good health, genomic inbreeding coefficients, MESH: Risk-Taking, 631/208/730, Autozygosit, homozygosity, Erfðarannsóknir, Medical Genetics, genomic inbreeding coefficient, MESH: Homozygote, Offspring, Science, Autozygosity, Blóðsifjar, 610 Medicine & health, Biology, INBREEDING DEPRESSION, HOMOZYGOSITY, FERTILITY, QUANTIFICATION, Physics and Astronomy(all), General Biochemistry, Genetics and Molecular Biology, Article, Association, 03 medical and health sciences, Risk-Taking, 360 Social problems & social services, Journal Article, Humans, ddc:610, Allele, Alleles, Medicinsk genetik, Genetic association study, MESH: Consanguinity, MESH: Body Size, MESH: Humans, Biochemistry, Genetics and Molecular Biology(all), MESH: Alleles, Haplotype, MESH: Fertility, General Chemistry, Brain Disorders, MESH: Inbreeding Depression, 030104 developmental biology, Fertility, Haplotypes, Genetic markers, lcsh:Q, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 3111 Biomedicine, Genetics and Molecular Biology(all)
Abstract

Publisher's version (útgefin grein)., In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding., This paper is the work of the ROHgen consortium. We thank the Sigma T2D Consortium, whose members are detailed in Supplementary Note 3. We thank the UK Biobank Resource, approved under application 19655; we acknowledge funding from the UK Medical Research Council Human Genetics Unit and MRC Doctoral Training Programme in Precision Medicine. We also thank Neil Robertson, Wellcome Trust Centre for Human Genetics, Oxford, for use of his author details management software, Authorial. Finally, we thank all the participants, researchers and funders of ROHgen cohorts. Cohort-specific acknowledgements are in Supplementary Data 2; personal acknowledgements and disclosures are in Supplementary Note 2. We thank Rachel Edwards for administrative assistance.

Published
2019
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8. On the genetic bias of the quarter of birth instrument

Author

Dinand Webbink, Cornelius A. Rietveld, Applied Economics, and Economics

Subjects
Earnings, business.industry, 05 social sciences, Economics, Econometrics and Finance (miscellaneous), Instrumental variable, Causal effect, Genetic data, Reproducibility of Results, Health and Retirement Study, Quarter (United States coin), Polymorphism, Single Nucleotide, Time, Socioeconomic Factors, 0502 economics and business, Income, Medicine, Educational Status, Humans, 050207 economics, Sex Distribution, business, 050205 econometrics, Demography
Abstract

Many studies in economics use quarter of birth as an instrument for identifying the causal effect of schooling on outcomes such as earnings and health. The key assumption in these studies is that people born in different quarters of the year do not differ systematically in their unobserved abilities. This study uses genetic data from the US Health and Retirement Study to analyze the validity of the quarter of birth instrument. We find some evidence that genetic factors influencing education are not randomly distributed over the year. However, these factors only slightly change the effect of quarter of birth on schooling.

Published
2016

9. Health and entrepreneurship in four Caribbean Basin countries

Author

Cornelius A. Rietveld, Jolanda Hessels, Peter van der Zwan, Henry Bailey, and Applied Economics

Subjects
Adult, Male, Economic growth, Entrepreneurship, Adolescent, Health Status, media_common.quotation_subject, Economics, Econometrics and Finance (miscellaneous), Sample (statistics), Young Adult, Caribbean region, Perception, Caribbean Basin, 0502 economics and business, Economics, Humans, Occupations, 050207 economics, Marketing, media_common, Self-efficacy, 05 social sciences, Business failure, Fear, Middle Aged, Self Efficacy, Caribbean Region, Socioeconomic Factors, Female, Developed country, 050203 business & management
Abstract

The literature dealing with health and entrepreneurship has focused on developed countries. We use a sample of almost 5000 business owners and wage-workers from four Caribbean Basin countries to study this relationship. Analyses are performed using data from the Global Entrepreneurship Monitor along with the Visual Analogue Scale of the EQ-5D-5L instrument as an overall health rating. The results show that business owners are healthier than wage-workers, which is in line with the findings from studies in developed countries. Furthermore, better health is associated with a lower likelihood for fear of business failure to be a deterrent to new business formation, a greater likelihood of self-belief in having the skills to run a business, and an increased recognition of start-up business opportunities among wage-workers. These positive associations between health and entrepreneurial perceptions provide new evidence about why less healthy individuals refrain from entrepreneurship. Finally, we find that the healthiest business owners run the companies with the highest growth expectations.

Published
2016
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10. The stature of the self-employed and its relation with earnings and satisfaction

Author

Peter van der Zwan, Jolanda Hessels, Cornelius A. Rietveld, and Applied Economics

Subjects
Adult, Employment, Male, Labour economics, Adolescent, media_common.quotation_subject, Economics, Econometrics and Finance (miscellaneous), Wage, Personal Satisfaction, Young Adult, Germany, Economics, Humans, Proxy (statistics), health care economics and organizations, Aged, media_common, Career Choice, Earnings, Entrepreneurship, Life satisfaction, Percentage point, Middle Aged, Body Height, Educational attainment, Socioeconomic Factors, Income, Female, Demographic economics, Self-employment, Social status
Abstract

Taller individuals have on average a higher socio-economic status than shorter individuals. In countries where entrepreneurs have high social status, we may therefore expect that entrepreneurs are taller than wage workers. Using data from the German Socio-Economic Panel (2002–2012), we find that a 1 cm increase in an individual's height raises the probability of being self-employed (the most common proxy for entrepreneurship) versus paid employed by 0.15 percentage points. Within the self-employed, the probability of being an employer is increased by 0.10 percentage points as a result of a 1 cm increase in height, whereas this increase is 0.05 percentage points for an own-account worker. This result corroborates the higher social status of employers compared to own-account workers. We find a height premium in earnings for self-employed and paid-employed individuals: an additional 1 cm in height is associated with a 0.39% increase in hourly earnings for paid employees and a 0.52% increase for self-employed individuals. Our analysis reveals that approximately one third of the height premium in earnings is explained by differences in educational attainment. We also establish the existence of a height premium in terms of work and life satisfaction, which is more pronounced for paid employees than for self-employed individuals.

Published
2015
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11. Genome-wide association study results for educational attainment aid in identifying genetic heterogeneity of schizophrenia

Author

Michel G. Nivard, Stefan Bonn, Hannelore Ehrenreich, Stephan Ripke, Casper A.P. Burik, Martin Begemann, Philipp Koellinger, Ronald de Vlaming, Vikas Bansal, Richard Karlsson Linnér, Aysu Okbay, Marina Mitjans, Cornelius A. Rietveld, Applied Economics, Economics, Amsterdam Neuroscience - Complex Trait Genetics, Biological Psychology, and Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep

Subjects
Male, 0301 basic medicine, Linkage disequilibrium, Candidate gene, Bipolar Disorder, General Physics and Astronomy, Genome-wide association study, genetics [Cognition Disorders], Linkage Disequilibrium, 0302 clinical medicine, Gene Frequency, genetics [Schizophrenia], SLITRK1 protein, human, lcsh:Science, genetics [Nerve Tissue Proteins], Genetics, 0303 health sciences, Multidisciplinary, Forkhead Transcription Factors, Middle Aged, SLITRK1, genetics [Membrane Proteins], Phenotype, Schizophrenia, genetics [Forkhead Transcription Factors], Educational Status, Female, ddc:500, SDG 4 - Quality Education, Adult, Adolescent, Science, Concordance, Nerve Tissue Proteins, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Article, General Biochemistry, Genetics and Molecular Biology, Genetic Heterogeneity, Young Adult, 03 medical and health sciences, mental disorders, medicine, Humans, Bipolar disorder, Allele frequency, Aged, 030304 developmental biology, Models, Genetic, Genetic heterogeneity, Assortative mating, Reproducibility of Results, Membrane Proteins, General Chemistry, medicine.disease, FOXO6 protein, human, 030104 developmental biology, lcsh:Q, Cognition Disorders, genetics [Bipolar Disorder], 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

Higher educational attainment (EA) is negatively associated with schizophrenia (SZ). However, recent studies found a positive genetic correlation between EA and SZ. We investigate possible causes of this counterintuitive finding using genome-wide association study results for EA and SZ (N = 443,581) and a replication cohort (1169 controls; 1067 cases) with deeply phenotyped SZ patients. We find strong genetic dependence between EA and SZ that cannot be explained by chance, linkage disequilibrium, or assortative mating. Instead, several genes seem to have pleiotropic effects on EA and SZ, but without a clear pattern of sign concordance. Using EA as a proxy phenotype, we isolate FOXO6 and SLITRK1 as novel candidate genes for SZ. Our results reveal that current SZ diagnoses aggregate over at least two disease subtypes: one part resembles high intelligence and bipolar disorder (BIP), while the other part is a cognitive disorder that is independent of BIP., Educational attainment and schizophrenia have a negative phenotypic relationship but show positive genetic correlation. Here, the authors study genetic dependence between the two traits and find that multiple genes have pleiotropic effects on both without a systematic pattern of sign concordance.

Published
2017
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12. Polygenic scores associated with educational attainment in adults predict educational achievement and ADHD symptoms in children

Author

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

Subjects
Netherlands Twin Register (NTR), Multifactorial Inheritance, genetic association, genotype, Academic achievement, Educational achievement, single nucleotide polymorphism, genetic variability, Genetics (clinical), Netherlands, child, article, symptom, academic achievement, Psychiatry and Mental health, priority journal, achievement test, Regression Analysis, Psychology, SDG 4 - Quality Education, Clinical psychology, Adult, phenotype, effect size, attention deficit disorder, gene frequency, educational status, Cellular and Molecular Neuroscience, reading, study skills, mental disorders, Genetics, medicine, Humans, ADHD, Attention deficit hyperactivity disorder, Achievement test, controlled study, human, Association (psychology), Genetic association, attention disturbance, language, School performance, medicine.disease, arithmetic, major clinical study, Polygenic scores, Educational attainment, gene linkage disequilibrium, Attention Deficit Disorder with Hyperactivity, Study skills
Abstract

The American Psychiatric Association estimates that 3 to 7 per cent of all school aged children are diagnosed with attention deficit hyperactivity disorder (ADHD). Even after correcting for general cognitive ability, numerous studies report a negative association between ADHD and educational achievement. With polygenic scores we examined whether genetic variants that have a positive influence on educational attainment have a protective effect against ADHD. The effect sizes from a large GWA meta-analysis of educational attainment in adults were used to calculate polygenic scores in an independent sample of 12-year-old children from the Netherlands Twin Register. Linear mixed models showed that the polygenic scores significantly predicted educational achievement, school performance, ADHD symptoms and attention problems in children. These results confirm the genetic overlap between ADHD and educational achievement, indicating that one way to gain insight into genetic variants responsible for variation in ADHD is to include data on educational achievement, which are available at a larger scale. (C) 2014 Wiley Periodicals, Inc.

Published
2014
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13. Meta-GWAS Accuracy and Power (MetaGAP) Calculator Shows that Hiding Heritability Is Partially Due to Imperfect Genetic Correlations across Studies

Author

Patrick J. F. Groenen, Magnus Johannesson, F. J.A. Van Rooij, Ronald de Vlaming, André G. Uitterlinden, Philipp Koellinger, Patrik K. E. Magnusson, Roy Thurik, Cornelius A. Rietveld, Aysu Okbay, Albert Hofman, Applied Economics, Epidemiology, Econometrics, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, and Management and Organisation

Subjects
0301 basic medicine, Cancer Research, Heredity, Restricted maximum likelihood, Genome-wide association study, law.invention, 0302 clinical medicine, Mathematical and Statistical Techniques, law, Missing heritability problem, Statistics, Range (statistics), Genetics (clinical), Genetics, 0303 health sciences, 030305 genetics & heredity, Genomics, Data Accuracy, Phenotypes, Genetic Mapping, Meta-analysis, Physical Sciences, Statistics (Mathematics), Research Article, lcsh:QH426-470, Variant Genotypes, Biology, Research and Analysis Methods, Genetic correlation, Statistical power, 03 medical and health sciences, Hybrids (Biology), Meta-Analysis as Topic, Genome-Wide Association Studies, Journal Article, Humans, Statistical Methods, Molecular Biology, Ecology, Evolution, Behavior and Systematics, Alleles, 030304 developmental biology, Biology and Life Sciences, Computational Biology, Human Genetics, Heritability, Genome Analysis, lcsh:Genetics, 030104 developmental biology, Calculator, Haplotypes, Genetic Loci, 030217 neurology & neurosurgery, Mathematics, Software, Meta-Analysis, Forecasting, Genome-Wide Association Study
Abstract

Large-scale genome-wide association results are typically obtained from a fixed-effects meta-analysis of GWAS summary statistics from multiple studies spanning different regions and/or time periods. This approach averages the estimated effects of genetic variants across studies. In case genetic effects are heterogeneous across studies, the statistical power of a GWAS and the predictive accuracy of polygenic scores are attenuated, contributing to the so-called ‘missing heritability’. Here, we describe the online Meta-GWAS Accuracy and Power (MetaGAP) calculator (available at www.devlaming.eu) which quantifies this attenuation based on a novel multi-study framework. By means of simulation studies, we show that under a wide range of genetic architectures, the statistical power and predictive accuracy provided by this calculator are accurate. We compare the predictions from the MetaGAP calculator with actual results obtained in the GWAS literature. Specifically, we use genomic-relatedness-matrix restricted maximum likelihood to estimate the SNP heritability and cross-study genetic correlation of height, BMI, years of education, and self-rated health in three large samples. These estimates are used as input parameters for the MetaGAP calculator. Results from the calculator suggest that cross-study heterogeneity has led to attenuation of statistical power and predictive accuracy in recent large-scale GWAS efforts on these traits (e.g., for years of education, we estimate a relative loss of 51–62% in the number of genome-wide significant loci and a relative loss in polygenic score R2 of 36–38%). Hence, cross-study heterogeneity contributes to the missing heritability., Author Summary Large-scale genome-wide association studies are uncovering the genetic architecture of traits which are affected by many genetic variants. In such efforts, one typically meta-analyzes association results from multiple studies spanning different regions and/or time periods. Results from such efforts do not yet capture a large share of the heritability. The origins of this so-called ‘missing heritability’ have been strongly debated. One factor exacerbating the missing heritability is heterogeneity in the effects of genetic variants across studies. The effect of this type of heterogeneity on statistical power to detect associated genetic variants and the accuracy of polygenic predictions is poorly understood. In the current study, we derive the precise effects of heterogeneity in genetic effects across studies on both the statistical power to detect associated genetic variants as well as the accuracy of polygenic predictions. We present an online calculator, available at www.devlaming.eu, which accounts for these effects. By means of this calculator, we show that imperfect genetic correlations between studies substantially decrease statistical power and predictive accuracy and, thereby, contribute to the missing heritability. The MetaGAP calculator helps researchers to gauge how sensitive their results will be to heterogeneity in genetic effects across studies. If strong heterogeneity is expected, random-effects meta-analysis methods should be used instead of fixed-effects methods.

Published
2017
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14. Serum testosterone levels in males are not associated with entrepreneurial behavior in two independent observational studies

Author

Patrick J. F. Groenen, Frank J. A. van Rooij, Fernando Rivadeneira, Robin Haring, Henri Wallaschofski, Albert Hofman, Frank H. de Jong, Thomas Kohlmann, Roy Thurik, Philipp Koellinger, Matthias Nauck, Sebastian E. Baumeister, André G. Uitterlinden, Cornelius A. Rietveld, Matthijs J. H. M. van der Loos, Economics, Amsterdam Neuroscience - Complex Trait Genetics, Management and Organisation, Applied Economics, Erasmus School of Economics, Econometrics, Epidemiology, Internal Medicine, and ABS Other Research (FEB)

Subjects
Male, medicine.medical_specialty, Globulin, Population, Experimental and Cognitive Psychology, Logistic regression, Free testosterone, Behavioral Neuroscience, Rotterdam Study, Sex hormone-binding globulin, Internal medicine, medicine, Humans, Testosterone, Self-employment, education, Aged, Non-sex hormone-binding globulin-bound testosterone, education.field_of_study, biology, Entrepreneurship, Testosterone (patch), Middle Aged, Cross-Sectional Studies, Endocrinology, Study of Health in Pomerania, biology.protein, Serum testosterone, Psychology, hormones, hormone substitutes, and hormone antagonists, Blood sampling
Abstract

Previous research has suggested a positive association between testosterone (T) and entrepreneurial behavior in males. However, this evidence was found in a study with a small sample size and has not been replicated. In the present study, we aimed to verify this association using two large, independent, population-based samples of males. We tested the association of T with entrepreneurial behavior, operationalized as self-employment, using data from the Rotterdam Study (N=587) and the Study of Health in Pomerania (N=1697). Total testosterone (TT) and sex hormone-binding globulin (SHBG) were measured in the serum. Free testosterone (FT), non-SHBG-bound T (non-SHBG-T), and the TT/SHBG ratio were calculated and used as measures of bioactive serum T, in addition to TT adjusted for SHBG. Using logistic regression models, we found no significant associations between any of the serum T measures and self-employment in either of the samples. To our knowledge, this is the first large-scale study on the relationship between serum T and entrepreneurial behavior.

Published
2013
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15. 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
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16. Genetic variants linked to education predict longevity

Author

Chris Power, Gail Davies, Ilaria Gandin, Panagiotis Deloukas, Jennifer E. Huffman, Pascal Timshel, Albert V. Smith, A. Kong, Paul Lichtenstein, Joseph K. Pickrell, Philipp Koellinger, P. L. De Jager, Reedik Mägi, G. B. Chen, Neil Pendleton, B. V. Halldórsson, George Dedoussis, Antti-Pekka Sarin, Natalia Pervjakova, Veikko Salomaa, Simona Vaccargiu, Ozren Polasek, K. H. Jöckel, Elisabeth Steinhagen-Thiessen, Y. Milaneschi, Jessica D. Faul, Patricia A. Boyle, Patrik K. E. Magnusson, Igor Rudan, Christopher P. Nelson, Vilmundur Gudnason, John Attia, Jürgen Wellmann, Kristi Läll, Konstantin Strauch, Stuart J. Ritchie, Markus Perola, Nicola Pirastu, Klaus Bønnelykke, Robert Karlsson, R. de Vlaming, Liisa Keltigangas-Jarvinen, Thomas Meitinger, Riccardo E. Marioni, Anu Loukola, Barbera Franke, Reinhold Schmidt, Maël Lebreton, Sven Oskarsson, E. Mihailov, Harm-Jan Westra, David R. Weir, Aldi T. Kraja, Niek Verweij, Peter M. Visscher, Hans-Jörgen Grabe, Johannes H. Brandsma, Mark Adams, R. J. Scott, G. Thorleifsson, Tõnu Esko, Mika Kähönen, Saskia P. Hagenaars, Patrick Turley, Johannes Waage, Peter Lichtner, Dragana Vuckovic, Antonietta Robino, Henry Völzke, Lydia Quaye, C. de Leeuw, Marika Kaakinen, Wei Zhao, Abdel Abdellaoui, Reka Nagy, Pedro Marques-Vidal, Johan G. Eriksson, Alan F. Wright, Andres Metspalu, Lavinia Paternoster, Momoko Horikoshi, Jan A. Staessen, Tarunveer S. Ahluwalia, Tian Liu, Martin Kroh, Aldo Rustichini, Giorgia Girotto, Cristina Venturini, Lili Milani, Jennifer A. Smith, Ginevra Biino, Tessel E. Galesloot, Michael A. Horan, Gerardus A. Meddens, James F. Wilson, Francesco Cucca, Peter Vollenweider, Erika Salvi, P. J. van der Most, Jari Lahti, Campbell A, David Laibson, Andrew Bakshi, Wolfgang Hoffmann, Tomi Mäki-Opas, Andreas J. Forstner, C M van Duijn, Nicholas G. Martin, Jonathan Marten, Ute Bültmann, Olli T. Raitakari, David A. Bennett, A.G. Uitterlinden, J. E. De Neve, Ingrid B. Borecki, WD Hill, Bo Jacobsson, Antti Latvala, Katri Räikkönen, Michael B. Miller, Jonathan P. Beauchamp, S. J. van der Lee, Ilja Demuth, Stavroula Kanoni, Veronique Vitart, Elina Hyppönen, N. Eklund, Francesco P. Cappuccio, Robert F. Krueger, Maria Pina Concas, Jaime Derringer, F. J.A. Van Rooij, Helena Schmidt, Patrick J. F. Groenen, Valur Emilsson, Rico Rueedi, Aysu Okbay, Georg Homuth, Edith Hofer, W. E. R. Ollier, Hannah Campbell, Paolo Gasparini, Mark Alan Fontana, Magnus Johannesson, Seppo Koskinen, Christopher F. Chabris, Jouke-Jan Hottenga, Christine Meisinger, Kari Stefansson, Jun Ding, Tia Sorensen, Brenda W.J.H. Penninx, Michelle N. Meyer, James J. Lee, Diego Vozzi, Gonneke Willemsen, K. Petrovic, Sarah E. Medland, Mary F. Feitosa, Henning Tiemeier, L. J. Launer, William G. Iacono, Massimo Mangino, Tune H. Pers, S. E. Baumeister, Christopher Oldmeadow, Grant W. Montgomery, Marjo-Riitta Järvelin, Jaakko Kaprio, Catharine R. Gale, S.F.W. Meddens, Kevin Thom, Klaus Berger, Pablo V. Gejman, Lude Franke, Gyda Bjornsdottir, Daniel J. Benjamin, Steven F. Lehrer, Krista Fischer, Alan R. Sanders, S. Ulivi, Katharina E. Schraut, Tim D. Spector, Amy Hofman, Matt McGue, Terho Lehtimäki, D. C. Liewald, Hans Bisgaard, L. Eisele, Astanand Jugessur, George Davey Smith, T.B. Harris, A.R. Thurik, Cornelius A. Rietveld, David Schlessinger, Z. Kutalik, David J. Porteous, Lynne J. Hocking, N J Timpson, A. Palotie, Lambertus A. Kiemeney, Ian J. Deary, Sharon L.R. Kardia, Peter K. Joshi, Nilesh J. Samani, Michael A. Province, Börge Schmidt, Richa Gupta, Carmen Amador, Erin B. Ware, Joyce Y. Tung, Ioanna-Panagiota Kalafati, Lars Bertram, Caroline Hayward, P. van der Harst, Penelope A. Lind, Kadri Kaasik, N.A. Furlotte, Sarah E. Harris, B. St Pourcain, Susan M. Ring, Zhihong Zhu, Alexander Teumer, Behrooz Z. Alizadeh, Judith M. Vonk, Blair H. Smith, A Payton, Wouter J. Peyrot, Jacob Gratten, Douglas F. Levinson, C Gieger, Leanne M. Hall, Andrew Heath, Mario Pirastu, Peter Eibich, Nancy L. Pedersen, Ronny Myhre, Antonio Terracciano, David M. Evans, Raymond A. Poot, Uwe Völker, Dorret I. Boomsma, Clemens Baumbach, Unnur Thorsteinsdottir, Ivana Kolcic, Jia-Shu Yang, Dalton Conley, A. A. Vinkhuyzen, Danielle Posthuma, Karl-Oskar Lindgren, Olga Rostapshova, Jonas Bacelis, Daniele Cusi, Yong Qian, Bjarni Gunnarsson, George McMahon, Elizabeth G. Holliday, Pamela A. F. Madden, David A. Hinds, David Cesarini, Jianxin Shi, Najaf Amin, Dale R. Nyholt, Applied Economics, Epidemiology, Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Groningen Research Institute for Asthma and COPD (GRIAC), Aletta Jacobs School of Public Health, Public Health Research (PHR), Stem Cell Aging Leukemia and Lymphoma (SALL), Cardiovascular Centre (CVC), Amsterdam Neuroscience - Complex Trait Genetics, Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, EMGO - Mental health, Complex Trait Genetics, Biological Psychology, Marioni, RE, Ritchie, SJ, Joshi, PK, Hagenaars, SP, Hypponen, E, Benjamin, DJ, Social Science Genetic Association Consortium, Marioni, Re, Ritchie, Sj, Joshi, Pk, Hagenaars, Sp, Okbay, A, Fischer, K, Adams, Mj, Hill, Wd, Davies, G, Nagy, R, Amador, C, Läll, K, Metspalu, A, Liewald, Dc, Campbell, A, Wilson, Jf, Hayward, C, Esko, T, Porteous, Dj, Gale, Cr, Deary, Ij, Beauchamp, Jp, Fontana, Ma, Lee, Jj, Pers, Th, Rietveld, Ca, Turley, P, Chen, Gb, Emilsson, V, Meddens, Sf, Oskarsson, S, Pickrell, Jk, Thom, K, Timshel, P, de Vlaming, R, Abdellaoui, A, Ahluwalia, T, Bacelis, J, Baumbach, C, Bjornsdottir, G, Brandsma, Jh, Concas, MARIA PINA, Derringer, J, Furlotte, Na, Galesloot, Te, Girotto, Giorgia, Gupta, R, Hall, Lm, Harris, Se, Hofer, E, Horikoshi, M, Huffman, Je, Kaasik, K, Kalafati, Ip, Karlsson, R, Kong, A, Lahti, J, van der Lee, Sj, de Leeuw, C, Lind, Pa, Lindgren, Ko, Liu, T, Mangino, M, Marten, J, Mihailov, E, Miller, Mb, van der Most, Pj, Oldmeadow, C, Payton, A, Pervjakova, N, Peyrot, Wj, Qian, Y, Raitakari, O, Rueedi, R, Salvi, E, Schmidt, B, Schraut, Ke, Shi, J, Smith, Av, Poot, Ra, St Pourcain, B, Teumer, A, Thorleifsson, G, Verweij, N, Vuckovic, Dragana, Wellmann, J, Westra, Hj, Yang, J, Zhao, W, Zhu, Z, Alizadeh, Bz, Amin, N, Bakshi, A, Baumeister, Se, Biino, G, Bønnelykke, K, Boyle, Pa, Campbell, H, Cappuccio, Fp, De Neve, Je, Deloukas, P, Demuth, I, Ding, J, Eibich, P, Eisele, L, Eklund, N, Evans, Dm, Faul, Jd, Feitosa, Mf, Forstner, Aj, Gandin, Ilaria, Gunnarsson, B, Halldórsson, Bv, Harris, Tb, Heath, Ac, Hocking, Lj, Holliday, Eg, Homuth, G, Horan, Ma, Hottenga, Jj, de Jager, Pl, Jugessur, A, Kaakinen, Ma, Kähönen, M, Kanoni, S, Keltigangas Järvinen, L, Kiemeney, La, Kolcic, I, Koskinen, S, Kraja, At, Kroh, M, Kutalik, Z, Latvala, A, Launer, Lj, Lebreton, Mp, Levinson, Df, Lichtenstein, P, Lichtner, P, Loukola, A, Madden, Pa, Mägi, R, Mäki Opas, T, Marques Vidal, P, Meddens, Ga, Mcmahon, G, Meisinger, C, Meitinger, T, Milaneschi, Y, Milani, L, Montgomery, Gw, Myhre, R, Nelson, Cp, Nyholt, Dr, Ollier, We, Palotie, A, Paternoster, L, Pedersen, Nl, Petrovic, Ke, Räikkönen, K, Ring, Sm, Robino, Antonietta, Rostapshova, O, Rudan, I, Rustichini, A, Salomaa, V, Sanders, Ar, Sarin, Ap, Schmidt, H, Scott, Rj, Smith, Bh, Smith, Ja, Staessen, Ja, Steinhagen Thiessen, E, Strauch, K, Terracciano, A, Tobin, Md, Ulivi, Sheila, Vaccargiu, S, Quaye, L, van Rooij, Fj, Venturini, C, Vinkhuyzen, Aa, Völker, U, Völzke, H, Vonk, Jm, Vozzi, Diego, Waage, J, Ware, Eb, Willemsen, G, Attia, Jr, Bennett, Da, Berger, K, Bertram, L, Bisgaard, H, Boomsma, Di, Borecki, Ib, Bultmann, U, Chabris, Cf, Cucca, F, Cusi, D, Dedoussis, Gv, van Duijn, Cm, Eriksson, Jg, Franke, B, Franke, L, Gasparini, Paolo, Gejman, Pv, Gieger, C, Grabe, Hj, Gratten, J, Groenen, Pj, Gudnason, V, van der Harst, P, Hinds, Da, Hoffmann, W, Iacono, Wg, Jacobsson, B, Järvelin, Mr, Jöckel, Kh, Kaprio, J, Kardia, Sl, Lehtimäki, T, Lehrer, Sf, Magnusson, Pk, Martin, Ng, Mcgue, M, Pendleton, N, Penninx, Bw, Perola, M, Pirastu, Nicola, Pirastu, M, Polasek, O, Posthuma, D, Power, C, Province, Ma, Samani, Nj, Schlessinger, D, Schmidt, R, Sørensen, Ti, Spector, Td, Stefansson, K, Thorsteinsdottir, U, Thurik, Ar, Timpson, Nj, Tiemeier, H, Tung, Jy, Uitterlinden, Ag, Vitart, V, Vollenweider, P, Weir, Dr, Wright, Af, Conley, Dc, Krueger, Rf, Smith, Gd, Hofman, A, Laibson, Di, Medland, Se, Meyer, Mn, Johannesson, M, Visscher, Pm, Koellinger, Pd, Cesarini, D, and Benjamin, Dj

Subjects
Netherlands Twin Register (NTR), 0301 basic medicine, Male, Parents, education: longevity: prediction: polygenic score [genetics], Multifactorial Inheritance, polygenic, Lebenserwartung, Cohort Studies, 0302 clinical medicine, Databases, Genetic, Medicine, genetics, polygenic score, longevity, education, gene, Soziales und Gesundheit, media_common, Aged, 80 and over, education, Multidisciplinary, Longevity, Middle Aged, Biobank, humanities, 3. Good health, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Cohort, Educational Status, Female, Cohort study, Estonia, education, longevity, polygenic, Offspring, media_common.quotation_subject, Kultursektor, Prognose, Lernen, Lower risk, Education, 03 medical and health sciences, longevity, SDG 3 - Good Health and Well-being, Commentaries, Polygenic score, Journal Article, Genetics, Humans, Non-Profit-Sektor, Genetic Association Studies, Aged, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], business.industry, ta1184, Genetic Variation, prediction, Educational attainment, United Kingdom, Gesundheitsstatistik, 030104 developmental biology, Genetic epidemiology, Scotland, Gesundheitszustand, Genetische Forschung, business, Prediction, Bildung, 030217 neurology & neurosurgery, Demography
Abstract

Educational attainment is associated with many health outcomes, including longevity. It is also known to be substantially heritable. Here, we used data from three large genetic epidemiology cohort studies (Generation Scotland, n = ∼17,000; UK Biobank, n = ∼115,000; and the Estonian Biobank, n = ∼6,000) to test whether education-linked genetic variants can predict lifespan length. We did so by using cohort members' polygenic profile score for education to predict their parents' longevity. Across the three cohorts, meta-analysis showed that a 1 SD higher polygenic education score was associated with ∼2.7% lower mortality risk for both mothers (total n deaths = 79,702) and ∼2.4% lower risk for fathers (total n deaths = 97,630). On average, the parents of offspring in the upper third of the polygenic score distribution lived 0.55 y longer compared with those of offspring in the lower third. Overall, these results indicate that the genetic contributions to educational attainment are useful in the prediction of human longevity. Marioni RE, Ritchie SJ, Joshi PK, Hagenaars SP, Okbay A, Fischer K, Adams MJ, Hill WD, Davies G, Social Science Genetic Association Consortium, Nagy R, Amador C, Läll K, Metspalu A, Liewald DC, Campbell A, Wilson JF, Hayward C, Esko T, Porteous DJ, Proceedings of the National Academy of Sciences of the United States of America, 2016, vol. 113, no. 47, pp. 13366-13371, 2016 Refereed/Peer-reviewed

Published
2016
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17. Pleiotropy-robust Mendelian Randomization

Author

Hans van Kippersluis and Cornelius A. Rietveld

Subjects
0301 basic medicine, Epidemiology, Genome-wide association study, Biology, 03 medical and health sciences, 0302 clinical medicine, 0502 economics and business, Pleiotropism, Genetic variation, Mendelian randomization, Methods, Econometrics, Genetic Pleiotropy, Humans, Disease, Genetic Predisposition to Disease, 030212 general & internal medicine, 050207 economics, 030304 developmental biology, Estimation, 0303 health sciences, 05 social sciences, Causal effect, Instrumental variable, Genetic variants, Genetic Variation, Estimator, Mendelian Randomization Analysis, General Medicine, Pleiotropy (drugs), 030104 developmental biology
Abstract

BackgroundThe potential of Mendelian Randomization studies is rapidly expanding due to (i) the growing power of GWAS meta-analyses to detect genetic variants associated with several exposures, and (ii) the increasing availability of these genetic variants in large-scale surveys. However, without a proper biological understanding of the pleiotropic working of genetic variants, a fundamental assumption of Mendelian Randomization (the exclusion restriction) can always be contested.MethodsWe build upon and synthesize recent advances in the econometric literature on instrumental variables (IV) estimation that test and relax the exclusion restriction. Our Pleiotropy-robust Mendelian Randomization (PRMR) method first estimates the degree of pleiotropy, and in turn corrects for it. If a sample exists for which the genetic variants do not affect the exposure, and pleiotropic effects are homogenous, PRMR obtains unbiased estimates of causal effects in case of pleiotropy.ResultsSimulations show that existing MR methods produce biased estimators for realistic forms of pleiotropy. Under the aforementioned assumptions, PRMR produces unbiased estimators. We illustrate the practical use of PRMR by estimating the causal effect of (i) cigarettes smoked per day on Body Mass Index (BMI); (ii) prostate cancer on self-reported health, and (iii) educational attainment on BMI in the UK Biobank data.ConclusionsPRMR allows for instrumental variables that violate the exclusion restriction due to pleiotropy, and corrects for pleiotropy in the estimation of the causal effect. If the degree of pleiotropy is unknown, PRMR can still be used as a sensitivity analysis.Key messagesIf genetic variants have pleiotropic effects, causal estimates of Mendelian Randomization studies will be biased.Pleiotropy-robust Mendelian Randomization (PRMR) produces unbiased causal estimates in case (i) a subsample can be identified for which the genetic variants do not affect the exposure, and (ii) pleiotropic effects are homogenous.If such a subsample does not exist, PRMR can still routinely be reported as a sensitivity analysis in any MR analysis.If pleiotropic effects are not homogenous, PRMR can be used as an informal test to gauge the exclusion restriction.

Published
2016
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18. Genome-wide association study identifies 74 loci associated with educational attainment

Author

K. Petrovic, Massimo Mangino, Daniele Cusi, Ozren Polasek, Rodney J. Scott, Yong Qian, Aysu Okbay, Jari Lahti, Bjarni Gunnarsson, George McMahon, Elizabeth G. Holliday, Thomas Meitinger, Frank J. A. van Rooij, Mika Kähönen, Martin Kroh, Ian J. Deary, Neil Pendleton, Pamela A. F. Madden, David J. Porteous, Lambertus A. Kiemeney, Sven Oskarsson, Edith Hofer, Robert F. Krueger, Olga Rostapshova, Georg Homuth, Paolo Gasparini, Aldo Rustichini, Sarah E. Medland, Christian Gieger, Veronique Vitart, Nicholas J. Timpson, George Dedoussis, Joseph K. Pickrell, Christopher Oldmeadow, Aldi T. Kraja, Johan G. Eriksson, Lydia Quaye, William G. Iacono, Danielle Posthuma, George Davey Smith, Karl-Oskar Lindgren, David C. Liewald, Pim van der Harst, Börge Schmidt, Christine Power, Francesco P. Cappuccio, Francesco Cucca, Simona Vaccargiu, Joyce Y. Tung, Aarno Palotie, Natalia Pervjakova, Jonas Bacelis, Jouke-Jan Hottenga, Helena Schmidt, Kari Stefansson, Tamara B. Harris, Momoko Horikoshi, Lude Franke, Wolfgang Hoffmann, Ingrid B. Borecki, William E R Ollier, Johannes Waage, Andreas J. Forstner, Caroline Hayward, Penelope A. Lind, Patricia A. Boyle, Kadri Kaasik, Jian Yang, Gerardus A. Meddens, Antti Latvala, John Attia, Pascal Timshel, Vilmundur Gudnason, Maël Lebreton, Valur Emilsson, James F. Wilson, Jonathan Marten, Ute Bültmann, Erika Salvi, Olli T. Raitakari, Peter M. Visscher, Niek Verweij, Elisabeth Steinhagen-Thiessen, Cristina Venturini, Lili Milani, Tessel E. Galesloot, Kevin Thom, Klaus Berger, Paul Lichtenstein, Tian Liu, Philipp Koellinger, Riccardo E. Marioni, Marjo-Riitta Järvelin, Clemens Baumbach, Unnur Thorsteinsdottir, Magnus Johannesson, Susan M. Ring, David A. Bennett, Anu Loukola, Hans-Jörgen Grabe, Jan A. Staessen, Igor Rudan, Ginevra Biino, Nicholas G. Martin, Jingyun Yang, Anna A. E. Vinkhuyzen, Katri Räikkönen, Zhihong Zhu, Gudmar Thorleifsson, Mary F. Feitosa, Ivana Kolcic, Alexander Teumer, Jaakko Kaprio, David Schlessinger, Katharina E. Schraut, Konstantin Strauch, Ilja Demuth, Albert V. Smith, Juergen Wellmann, Jennifer E. Huffman, Panos Deloukas, Mario Pirastu, Reedik Mägi, Maria Pina Concas, Jaime Derringer, Patrick J. F. Groenen, Henry Völzke, Wei Zhao, Abdel Abdellaoui, Andres Metspalu, Nicholas A. Furlotte, Christopher P. Nelson, Barbara Franke, Steven F. Lehrer, Patrick Turley, Tõnu Esko, Jun Ding, Pedro Marques-Vidal, S. Fleur W. Meddens, Zoltán Kutalik, Gonneke Willemsen, Andrew C. Heath, Michelle N. Meyer, James J. Lee, Roy Thurik, Antonietta Robino, Henning Tiemeier, Grant W. Montgomery, C. deLeeuw, Astanand Jugessur, Antti-Pekka Sarin, Veikko Salomaa, Dalton Conley, Tim D. Spector, Sebastian E. Baumeister, Gyda Bjornsdottir, Lavinia Paternoster, Tune H. Pers, Jacob Gratten, Martin D. Tobin, Daniel J. Benjamin, Douglas F. Levinson, Stavroula Kanoni, Elina Hyppönen, David R. Weir, Peter J. van der Most, Terho Lehtimäki, David A. Hinds, Pablo V. Gejman, Uwe Völker, Cornelia M. van Duijn, Karl-Heinz Jöckel, Bjarni V. Halldorsson, Markus Perola, Nicola Pirastu, Klaus Bønnelykke, Robert Karlsson, David Cesarini, Michael A. Province, Jianxin Shi, Najaf Amin, Dale R. Nyholt, Lenore J. Launer, Nilesh J. Samani, Sven J. van der Lee, Dorret I. Boomsma, Harry Campbell, Peter Vollenweider, Liisa Keltigangas-Jarvinen, David Laibson, Ronald de Vlaming, Lynne J. Hocking, Christopher F. Chabris, Blair H. Smith, Gail Davies, Niina Eklund, Ioanna P. Kalafati, Bo Jacobsson, Sheila Ulivi, Alan F. Wright, Sarah E. Harris, Mark Alan Fontana, Diego Vozzi, Tomi Mäki-Opas, Albert Hofman, Hans Bisgaard, Andrew Bakshi, Marika Kaakinen, Johannes H. Brandsma, Christa Meisinger, Ilaria Gandin, Tarunveer S. Ahluwalia, Jennifer A. Smith, Beate St Pourcain, Rico Rueedi, Lewin Eisele, Michael B. Miller, Brenda W.J.H. Penninx, Alan R. Sanders, Thorkild I. A. Sørensen, André G. Uitterlinden, Cornelius A. Rietveld, Peter Lichtner, Dragana Vuckovic, Giorgia Girotto, Behrooz Z. Alizadeh, Reinhold Schmidt, Raymond A. Poot, Judith M. Vonk, Antony Payton, Wouter J. Peyrot, Augustine Kong, Y. Milaneschi, Jessica D. Faul, Patrik K. E. Magnusson, Antonio Terracciano, David M. Evans, Sharon L.R. Kardia, Peter K. Joshi, Michael A. Horan, Matt McGue, Richa Gupta, Jonathan P. Beauchamp, Peter Eibich, Erin B. Ware, Lars Bertram, Philip L. De Jager, Nancy L. Pedersen, Ronny Myhre, Guo-Bo Chen, Harm-Jan Westra, Jan-Emmanuel De Neve, Evelin Mihailov, Leanne M. Hall, Seppo Koskinen, Rush University Medical Center [Chicago], Department of Epidemiology [Rotterdam], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Helmholtz-Zentrum München (HZM), University of Queensland [Brisbane], Erasmus University Rotterdam, Universidad de Navarra [Pamplona] (UNAV), National Institute for Health and Welfare [Helsinki], Institute for Molecular Medicine Finland [Helsinki] (FIMM), Helsinki Institute of Life Science (HiLIFE), Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Consiglio Nazionale delle Ricerche (CNR), Montpellier Research in Management (MRM), 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), University of Bristol [Bristol], Queensland Institute of Medical Research, Massachusetts General Hospital [Boston], Medical University Graz, Institut des Sciences Moléculaires (ISM), 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), King‘s College London, Tampere University Hospital, University of Turku, AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Edinburgh, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Imperial College London, Reykjavík University, Donders Institute for Brain, Cognition and Behaviour, Radboud university [Nijmegen], Karolinska Institutet [Stockholm], Department of Health Sciences [Leicester], University of Leicester, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Department of Medical Epidemiology and Biostatistics (MEB), Dpt of Pharmacology and Personalised Medicine [Maastricht], Maastricht University [Maastricht], Florida State University [Tallahassee] (FSU), IT University of Copenhagen, University of Helsinki-University of Helsinki, 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), 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), Faculteit Economie en Bedrijfskunde, Microeconomics (ASE, FEB), LifeLines Cohort Study, Alizadeh, BZ., de Boer, RA., Boezen, HM., Bruinenberg, M., Franke, L., van der Harst, P., Hillege, HL., van der Klauw, MM., Navis, G., Ormel, J., Postma, DS., Rosmalen, JG., Slaets, JP., Snieder, H., Stolk, RP., Wolffenbuttel, BH., Wijmenga, C., Applied Economics, Cell biology, Epidemiology, Erasmus MC other, Econometrics, Child and Adolescent Psychiatry / Psychology, Psychiatry, Internal Medicine, EMGO+ - Mental Health, Complex Trait Genetics, Biological Psychology, Functional Genomics, Economics, Amsterdam Neuroscience - Complex Trait Genetics, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Groningen Research Institute for Asthma and COPD (GRIAC), Public Health Research (PHR), Cardiovascular Centre (CVC), Life Course Epidemiology (LCE), Stem Cell Aging Leukemia and Lymphoma (SALL), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Okbay, Aysu, Beauchamp, Jonathan P., Fontana, Mark Alan, Lee, James J., Pers, Tune H., Rietveld, Cornelius A., Turley, Patrick, Chen, Guo Bo, Emilsson, Valur, Meddens, S. Fleur W., Oskarsson, Sven, Pickrell, Joseph K., Thom, Kevin, Timshel, Pascal, De Vlaming, Ronald, Abdellaoui, Abdel, Ahluwalia, Tarunveer S., Bacelis, Jona, Baumbach, Clemen, Bjornsdottir, Gyda, Brandsma, Johannes H., Concas, MARIA PINA, Derringer, Jaime, Furlotte, Nicholas A., Galesloot, Tessel E., Girotto, Giorgia, Gupta, Richa, Hall, Leanne M., Harris, Sarah E., Hofer, Edith, Horikoshi, Momoko, Huffman, Jennifer E., Kaasik, Kadri, Kalafati, Ioanna P., Karlsson, Robert, Kong, Augustine, Lahti, Jari, Van Der Lee, Sven J., Deleeuw, Christiaan, Lind, Penelope A., Lindgren, Karl Oskar, Liu, Tian, Mangino, Massimo, Marten, Jonathan, Mihailov, Evelin, Miller, Michael B., Van Der Most, Peter J., Oldmeadow, Christopher, Payton, Antony, Pervjakova, Natalia, Peyrot, Wouter J., Qian, Yong, Raitakari, Olli, Rueedi, Rico, Salvi, Erika, Schmidt, Börge, Schraut, Katharina E., Shi, Jianxin, Smith, Albert V., Poot, Raymond A., St Pourcain, Beate, Teumer, Alexander, Thorleifsson, Gudmar, Verweij, Niek, Vuckovic, Dragana, Wellmann, Juergen, Westra, Harm Jan, Yang, Jingyun, Zhao, Wei, Zhu, Zhihong, Alizadeh, Behrooz Z., Amin, Najaf, Bakshi, Andrew, Baumeister, Sebastian E., Biino, Ginevra, Bønnelykke, Klau, Boyle, Patricia A., Campbell, Harry, Cappuccio, Francesco P., Davies, Gail, De Neve, Jan Emmanuel, Deloukas, Pano, Demuth, Ilja, Ding, Jun, Eibich, Peter, Eisele, Lewin, Eklund, Niina, Evans, David M., Faul, Jessica D., Feitosa, Mary F., Forstner, Andreas J., Gandin, Ilaria, Gunnarsson, Bjarni, Halldórsson, Bjarni V., Harris, Tamara B., Holliday, Elizabeth G., Heath, Andrew C., Hocking, Lynne J., Homuth, Georg, Horan, Michael A., Hottenga, Jouke Jan, De Jager, Philip L., Joshi, Peter K., Jugessur, Astanand, Kaakinen, Marika A., Kähönen, Mika, Kanoni, Stavroula, Keltigangas Järvinen, Liisa, Kiemeney, Lambertus A. L. M., Kolcic, Ivana, Koskinen, Seppo, Kraja, Aldi T., Kroh, Martin, Kutalik, Zoltan, Latvala, Antti, Launer, Lenore J., Lebreton, Maël P., Levinson, Douglas F., Lichtenstein, Paul, Lichtner, Peter, Liewald, David C. M., Loukola, Anu, Madden, Pamela A., Mägi, Reedik, Mäki Opas, Tomi, Marioni, Riccardo E., Marques Vidal, Pedro, Meddens, Gerardus A., Mcmahon, George, Meisinger, Christa, Meitinger, Thoma, Milaneschi, Yusplitri, Milani, Lili, Montgomery, Grant W., Myhre, Ronny, Nelson, Christopher P., Nyholt, Dale R., Ollier, William E. R., Palotie, Aarno, Paternoster, Lavinia, Pedersen, Nancy L., Petrovic, Katja E., Porteous, David J., Raïkkönen, Katri, Ring, Susan M., Robino, Antonietta, Rostapshova, Olga, Rudan, Igor, Rustichini, Aldo, Salomaa, Veikko, Sanders, Alan R., Sarin, Antti Pekka, Schmidt, Helena, Scott, Rodney J., Smith, Blair H., Smith, Jennifer A., Staessen, Jan A., Steinhagen Thiessen, Elisabeth, Strauch, Konstantin, Terracciano, Antonio, Tobin, Martin D., Ulivi, Sheila, Vaccargiu, Simona, Quaye, Lydia, Van Rooij, Frank J. A., Venturini, Cristina, Vinkhuyzen, Anna A. E., Völker, Uwe, Völzke, Henry, Vonk, Judith M., Vozzi, Diego, Waage, Johanne, Ware, Erin B., Willemsen, Gonneke, Attia, John R., Bennett, David A., Berger, Klau, Bertram, Lar, Bisgaard, Han, Boomsma, Dorret I., Borecki, Ingrid B., Bültmann, Ute, Chabris, Christopher F., Cucca, Francesco, Cusi, Daniele, Deary, Ian J., Dedoussis, George V., Van Duijn, Cornelia M., Eriksson, Johan G., Franke, Barbara, Franke, Lude, Gasparini, Paolo, Gejman, Pablo V., Gieger, Christian, Grabe, Hans Jörgen, Gratten, Jacob, Groenen, Patrick J. F., Gudnason, Vilmundur, Van Der Harst, Pim, Hayward, Caroline, Hinds, David A., Hoffmann, Wolfgang, Hyppönen, Elina, Iacono, William G., Jacobsson, Bo, Järvelin, Marjo Riitta, Jöckel, Karl Heinz, Kaprio, Jaakko, Kardia, Sharon L. R., Lehtimäki, Terho, Lehrer, Steven F., Magnusson, Patrik K. E., Martin, Nicholas G., Mcgue, Matt, Metspalu, Andre, Pendleton, Neil, Penninx, Brenda W. J. H., Perola, Marku, Pirastu, Nicola, Pirastu, Mario, Polasek, Ozren, Posthuma, Danielle, Power, Christine, Province, Michael A., Samani, Nilesh J., Schlessinger, David, Schmidt, Reinhold, Sørensen, Thorkild I. A., Spector, Tim D., Stefansson, Kari, Thorsteinsdottir, Unnur, Thurik, A. Roy, Timpson, Nicholas J., Tiemeier, Henning, Tung, Joyce Y., Uitterlinden, André G., Vitart, Veronique, Vollenweider, Peter, Weir, David R., Wilson, James F., Wright, Alan F., Conley, Dalton C., Krueger, Robert F., Davey Smith, George, Hofman, Albert, Laibson, David I., Medland, Sarah E., Meyer, Michelle N., Yang, Jian, Johannesson, Magnu, Visscher, Peter M., Esko, Toñu, Koellinger, Philipp D., Cesarini, David, Benjamin, Daniel J., EMGO - Mental health, IOO, Human genetics, Beauchamp, Jonathan P, Lee, James JJ, Hypponen, Elina, and Benjamin, Daniel J

Subjects
0301 basic medicine, Netherlands Twin Register (NTR), Candidate gene, Bipolar Disorder, Medizin, Genome-wide association study, Genome-wide association studies, 0302 clinical medicine, Cognition, Alzheimer Disease, Brain, Computational Biology, Fetus, Gene Expression Regulation, Gene-Environment Interaction, Great Britain, Humans, Molecular Sequence Annotation, Polymorphism, Single Nucleotide, Schizophrenia, Educational Status, Genome-Wide Association Study, Medicine (all), Multidisciplinary, Fetu, tau, Gene–environment interaction, Soziales und Gesundheit, Genetics, [QFIN]Quantitative Finance [q-fin], HERITABILITY, General Commentary, Alzheimer's disease, Biobank, Phenotype, Multidisciplinary Sciences, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], educational attainment, Behavioural genetics, Science & Technology - Other Topics, Bildungsniveau, TRAITS, Human, General Science & Technology, Kultursektor, SNP, ta3111, Polymorphism, Single Nucleotide, Learning and memory, Alzheimer Disease/genetics, Bipolar Disorder/genetics, Brain/metabolism, Fetus/metabolism, Gene Expression Regulation/genetics, Polymorphism, Single Nucleotide/genetics, Schizophrenia/genetics, 03 medical and health sciences, ACHIEVEMENT, MD Multidisciplinary, Non-Profit-Sektor, QH426, Science & Technology, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], tauopathies, Data Science, gene, education, school, Heritability, Educational Statu, Educational attainment, United Kingdom, 030104 developmental biology, IQ, Genetische Forschung, Psychiatric disorders, Bildung, 030217 neurology & neurosurgery, LifeLines Cohort Study, Neuroscience
Abstract

Contains fulltext : 167137.pdf (Publisher’s version ) (Closed access) Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.

Published
2016
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19. 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
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20. On improving the credibility of candidate gene studies: A review of candidate gene studies published in Emotion

Author

Aysu Okbay, Cornelius A. Rietveld, Economics, Amsterdam Neuroscience - Complex Trait Genetics, and Applied Economics

Subjects
Candidate gene, Genetic Research, Emotions, Genetic variants, Replication, Guidelines as Topic, Computational biology, Candidate gene study, Power, Credibility, Trait, Model specification, Humans, Periodicals as Topic, Set (psychology), Psychology, Significance, General Psychology, Behavioural genetics, Genetic Association Studies, Behavioral Research
Abstract

The discovery of genetic variants associated with psychological traits deepens our knowledge about causes and consequences of individual differences. In psychology, the standard approach to identify these variants is the "candidate gene study." In a candidate gene study, a limited set of genetic variants is selected based on their hypothesized or known biological function, and these variants are tested for association with the psychological trait of interest. The successful replication of published candidate gene studies, however, is alarmingly scarce. In this article we describe the challenges to successfully identifying genetic associations, and review the candidate gene studies published in Emotion. We conclude that the implementation of 4 methodological guidelines developed by the Behavior Genetics Association for evaluating candidate gene studies will help to increase the credibility of candidate gene study findings.

Published
2015
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21. 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
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22. 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, 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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
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23. 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, George, Davey Smith, and Nicholas J, Timpson

Subjects
Adult, Male, Adolescent, Epidemiology, Intelligence, Polymorphism, Single Nucleotide, Genetics, Medicine and Health Sciences, Humans, Learning, Public and Occupational Health, Longitudinal Studies, Child, Genetic Association Studies, Lifecourse Epidemiology, Intelligence Tests, Biology and Life Sciences, Human Genetics, Socioeconomic Aspects of Health, Health Care, Child, Preschool, Genetic Epidemiology, Educational Status, Female, Mathematics, Genome-Wide Association Study, Research Article
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), p10(-10)) with more similar results (though in the opposite direction) in mathematics (0.042 SD (95%CI 0.004, 0.080), p = 0.030). Each additional adult educational attainment increasing allele was associated with 0.041 SD (95%CI 0.020, 0.063), p = 1.79×10(-04) and 0.028 SD (95%CI 0.007, 0.050), p = 0.01 increases in standardised SATS score for English and mathematics respectively. Educational attainment is a complex multifactorial behavioural trait which has not had heritable contributions to it fully characterised. We were able to apply the results from a large study of adult educational attainment to a study of child exam performance marking events in the process of learning rather than realised adult end product. Our results support evidence for common, small genetic contributions to educational attainment, but also emphasise the likely lifecourse nature of this genetic effect. Results here also, by an alternative route, suggest that existing methods for child examination are able to recognise early life variation likely to be related to ultimate educational attainment.

Published
2014

24. 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
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25. 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
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26. 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
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