TY - RPRT T1 - Genetic Fortune: Winning or Losing Education, Income, and Health Y1 - 2020 A1 - Kweon, Hyeokmoon A1 - Burik, Casper A1 - Richard Karlsson Linnér A1 - de Vlaming, Ronald A1 - Okbay, Aysu A1 - Martschenko, Daphne A1 - Harden, Kathryn A1 - DiPrete, Thomas A1 - Philipp D Koellinger KW - Education KW - Genetics KW - health KW - heritability KW - Income KW - Inequality KW - polygenic score AB - We study the effects of genetic endowments on inequalities in education, income, and health. Specifically, we conduct the first genome-wide association study (GWAS) of individual income, using data from individuals of European ancestries. We find that ≈10% of the variance in occupational wages can be attributed to genetic similarities between individuals who are only very distantly related to each other. Our GWAS (N = 282,963) identifies 45 approximately independent genetic loci for occupational wages, each with a tiny effect size (R 2<0.04%). An aggregated genetic score constructed from these GWAS results accounts for ≈1% of the variance in self-reported income in two independent samples (N = 29,440) and improves upon the variance captured by a genetic score obtained from previous GWAS results for educational attainment. A one-standard-deviation increase in our genetic score for occupational wages is associated with a 6–8% increase in self-reported hourly wages. We exploit random genetic differences between ~35,000 biological siblings to show that (i) roughly half of the covariance between our genetic score and socioeconomic outcomes is causal, (ii) genetic luck for higher income is linked with better health outcomes in late adulthood, and (iii) having a college degree partly mediates this relationship. We also demonstrate that the returns to schooling remain substantial even after controlling for genetic confounds, with an average of 8–11% higher hourly wages for each additional year of education obtained in a US sample. Thus, the implications of genetic endowments are malleable, for example, via policies targeting education. JF - Tinbergen Institue Discussion Paper PB - Tinbergen Institute CY - Amsterdam UR - https://papers.tinbergen.nl/20053.pdf ER - TY - JOUR T1 - Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals. JF - Nature Genetics Y1 - 2018 A1 - Lee, James J A1 - Wedow, Robbee A1 - Okbay, Aysu A1 - Kong, Edward A1 - Maghzian, Omeed A1 - Zacher, Meghan A1 - Nguyen-Viet, Tuan Anh A1 - Bowers, Peter A1 - Sidorenko, Julia A1 - Richard Karlsson Linnér A1 - Mark Alan Fontana A1 - Kundu, Tushar A1 - Lee, Chanwook A1 - Hui Liu A1 - Li, Ruoxi A1 - Royer, Rebecca A1 - Pascal N Timshel A1 - Walters, Raymond K A1 - Willoughby, Emily A A1 - Yengo, Loic A1 - Alver, Maris A1 - Bao, Yanchun A1 - Clark, David W A1 - Day, Felix R A1 - Furlotte, Nicholas A A1 - Joshi, Peter K A1 - Kathryn E Kemper A1 - Kleinman, Aaron A1 - Langenberg, Claudia A1 - Mägi, Reedik A1 - Joey W Trampush A1 - Verma, Shefali Setia A1 - Wu, Yang A1 - Lam, Max A1 - Jing Hua Zhao A1 - Zheng, Zhili A1 - Jason D Boardman A1 - Campbell, Harry A1 - Freese, Jeremy A1 - Kathleen Mullan Harris A1 - Caroline Hayward A1 - Herd, Pamela A1 - Kumari, Meena A1 - Lencz, Todd A1 - Luan, Jian'an A1 - Anil K. Malhotra A1 - Andres Metspalu A1 - Lili Milani A1 - Ong, Ken K A1 - Perry, John R B A1 - David J Porteous A1 - Ritchie, Marylyn D A1 - Smart, Melissa C A1 - Smith, Blair H A1 - Tung, Joyce Y A1 - Wareham, Nicholas J A1 - James F Wilson A1 - Jonathan P. Beauchamp A1 - Dalton C Conley A1 - Tõnu Esko A1 - Lehrer, Steven F A1 - Patrik K E Magnusson A1 - Oskarsson, Sven A1 - Pers, Tune H A1 - Matthew R Robinson A1 - Thom, Kevin A1 - Watson, Chelsea A1 - Chabris, Christopher F A1 - Meyer, Michelle N A1 - David I Laibson A1 - Yang, Jian A1 - Johannesson, Magnus A1 - Philipp D Koellinger A1 - Turley, Patrick A1 - Peter M Visscher A1 - Daniel J. Benjamin A1 - Cesarini, David KW - Adult KW - Aged KW - Aged, 80 and over KW - Cohort Studies KW - Educational Status KW - Female KW - Genome-Wide Association Study KW - Humans KW - Male KW - Middle Aged KW - Multifactorial Inheritance KW - Phenotype KW - Polymorphism, Single Nucleotide AB -

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

VL - 50 IS - 8 U1 - http://www.ncbi.nlm.nih.gov/pubmed/30038396?dopt=Abstract ER - TY - JOUR T1 - Genetic Heterogeneity in Depressive Symptoms Following the Death of a Spouse: Polygenic Score Analysis of the U.S. Health and Retirement Study JF - American Journal of Psychiatry Y1 - 2017 A1 - Benjamin W Domingue A1 - Hexuan Liu A1 - Okbay, Aysu A1 - Daniel W. Belsky KW - Bereavement KW - Depressive symptoms KW - Genetics AB - Objective: Experience of stressful life events is associated with risk of depression. Yet many exposed individuals do not become depressed. A controversial hypothesis is that genetic factors influence vulnerability to depression following stress. This hypothesis is often tested with a “diathesis-stress” model, in which genes confer excess vulnerability. The authors tested an alternative formulation of this model: genes may buffer against depressogenic effects of life stress. Method: The hypothesized genetic buffer was measured using a polygenic score derived from a published genome-wide association study of subjective well-being. The authors tested whether married older adults who had higher polygenic scores were less vulnerable to depressive symptoms following the death of their spouse compared with age-matched peers who had also lost their spouse and who had lower polygenic scores. Data were analyzed from 8,588 non-Hispanic white adults in the Health and Retirement Study (HRS), a population-representative longitudinal study of older adults in the United States. Results: HRS adults with higher well-being polygenic scores experienced fewer depressive symptoms during follow-up. Those who survived the death of their spouses (N=1,647) experienced a sharp increase in depressive symptoms following the death and returned toward baseline over the following 2 years. Having a higher well-being polygenic score buffered against increased depressive symptoms following a spouse’s death. Conclusions: The effects were small, and the clinical relevance is uncertain, although polygenic score analyses may provide clues to behavioral pathways that can serve as therapeutic targets. Future studies of gene-environment interplay in depression may benefit from focus on genetics discovered for putative protective factors. VL - 174 UR - http://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2017.16111209 IS - 10 JO - AJP ER - TY - JOUR T1 - Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses. JF - Nat Genet Y1 - 2016 A1 - Okbay, Aysu A1 - Baselmans, Bart M L A1 - De Neve, Jan-Emmanuel A1 - Turley, Patrick A1 - Nivard, Michel G A1 - Mark Alan Fontana A1 - Meddens, S Fleur W A1 - Richard Karlsson Linnér A1 - Cornelius A Rietveld A1 - Derringer, Jaime A1 - Gratten, Jacob A1 - Lee, James J A1 - Liu, Jimmy Z A1 - de Vlaming, Ronald A1 - Ahluwalia, Tarunveer S A1 - Buchwald, Jadwiga A1 - Cavadino, Alana A1 - Frazier-Wood, Alexis C A1 - Furlotte, Nicholas A A1 - Garfield, Victoria A1 - Geisel, Marie Henrike A1 - Gonzalez, Juan R A1 - Haitjema, Saskia A1 - Karlsson, Robert A1 - van der Laan, Sander W A1 - Ladwig, Karl-Heinz A1 - J. Lahti A1 - Sven J van der Lee A1 - Penelope A Lind A1 - Tian Liu A1 - Lindsay K Matteson A1 - Mihailov, Evelin A1 - Michael B Miller A1 - Minica, Camelia C A1 - Ilja M Nolte A1 - Dennis O Mook-Kanamori A1 - van der Most, Peter J A1 - Christopher J Oldmeadow A1 - Qian, Yong A1 - Olli T Raitakari A1 - Rawal, Rajesh A1 - Realo, Anu A1 - Rueedi, Rico A1 - Schmidt, Börge A1 - Albert Vernon Smith A1 - Stergiakouli, Evie A1 - Toshiko Tanaka A1 - Kent D Taylor A1 - Wedenoja, Juho A1 - Jürgen Wellmann A1 - Westra, Harm-Jan A1 - Willems, Sara M A1 - Wei Zhao A1 - Amin, Najaf A1 - Bakshi, Andrew A1 - Patricia A. Boyle A1 - Cherney, Samantha A1 - Cox, Simon R A1 - Gail Davies A1 - Davis, Oliver S P A1 - Ding, Jun A1 - Nese Direk A1 - Eibich, Peter A1 - Emeny, Rebecca T A1 - Fatemifar, Ghazaleh A1 - Jessica Faul A1 - Luigi Ferrucci A1 - Andreas J Forstner A1 - Gieger, Christian A1 - Gupta, Richa A1 - Tamara B Harris A1 - Harris, Juliette M A1 - Holliday, Elizabeth G A1 - Jouke-Jan Hottenga A1 - Philip L de Jager A1 - Marika A Kaakinen A1 - Kajantie, Eero A1 - Karhunen, Ville A1 - Kolcic, Ivana A1 - Kumari, Meena A1 - Lenore J Launer A1 - Lude L Franke A1 - Li-Gao, Ruifang A1 - Koini, Marisa A1 - Loukola, Anu A1 - Marques-Vidal, Pedro A1 - Grant W Montgomery A1 - Mosing, Miriam A A1 - Paternoster, Lavinia A1 - Pattie, Alison A1 - Katja E Petrovic A1 - Pulkki-Raback, Laura A1 - Quaye, Lydia A1 - Katri Räikkönen A1 - Rudan, Igor A1 - Rodney J Scott A1 - Jennifer A Smith A1 - Angelina R Sutin A1 - Trzaskowski, Maciej A1 - Anna A E Vinkhuyzen A1 - Lei Yu A1 - Zabaneh, Delilah A1 - John R. Attia A1 - David A Bennett A1 - Klaus Berger A1 - Bertram, Lars A1 - Dorret I Boomsma A1 - Snieder, Harold A1 - Chang, Shun-Chiao A1 - Francesco Cucca A1 - Ian J Deary A1 - Cornelia M van Duijn A1 - Johan G Eriksson A1 - Bültmann, Ute A1 - Eco J. C. de Geus A1 - Groenen, Patrick J F A1 - Gudnason, Vilmundur A1 - Hansen, Torben A1 - Catharina A Hartman A1 - Haworth, Claire M A A1 - Caroline Hayward A1 - Andrew C Heath A1 - Hinds, David A A1 - Hyppönen, Elina A1 - Iacono, William G A1 - Järvelin, Marjo-Riitta A1 - Jöckel, Karl-Heinz A1 - Kaprio, Jaakko A1 - Sharon L R Kardia A1 - Keltikangas-Järvinen, Liisa A1 - Kraft, Peter A1 - Laura D Kubzansky A1 - Lehtimäki, Terho A1 - Patrik K E Magnusson A1 - Nicholas G Martin A1 - McGue, Matt A1 - Andres Metspalu A1 - Melinda C Mills A1 - de Mutsert, Renée A1 - Oldehinkel, Albertine J A1 - Pasterkamp, Gerard A1 - Nancy L Pedersen A1 - Plomin, Robert A1 - Polasek, Ozren A1 - Power, Christine A1 - Rich, Stephen S A1 - Rosendaal, Frits R A1 - Hester M. den Ruijter A1 - Schlessinger, David A1 - Schmidt, Helena A1 - Svento, Rauli A1 - Schmidt, Reinhold A1 - Alizadeh, Behrooz Z A1 - Thorkild I. A. Sørensen A1 - Timothy Spector A1 - Andrew Steptoe A1 - Antonio Terracciano A1 - A. Roy Thurik A1 - Nicholas J Timpson A1 - Henning Tiemeier A1 - André G Uitterlinden A1 - Vollenweider, Peter A1 - Wagner, Gert G A1 - David R Weir A1 - Yang, Jian A1 - Dalton C Conley A1 - Hofman, Albert A1 - Johannesson, Magnus A1 - David I Laibson A1 - Sarah E Medland A1 - Meyer, Michelle N A1 - Pickrell, Joseph K A1 - Tõnu Esko A1 - Krueger, Robert F A1 - Jonathan P. Beauchamp A1 - Philipp D Koellinger A1 - Daniel J. Benjamin A1 - Bartels, Meike A1 - Cesarini, David KW - Anxiety Disorders KW - Bayes Theorem KW - depression KW - Genome-Wide Association Study KW - Humans KW - Neuroticism KW - Phenotype KW - Polymorphism, Single Nucleotide AB -

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

VL - 48 IS - 6 U1 - http://www.ncbi.nlm.nih.gov/pubmed/27089181?dopt=Abstract ER - TY - JOUR T1 - Genome-wide association study identifies 74 loci associated with educational attainment. JF - Nature Y1 - 2016 A1 - Okbay, Aysu A1 - Jonathan P. Beauchamp A1 - Mark Alan Fontana A1 - Lee, James J A1 - Pers, Tune H A1 - Cornelius A Rietveld A1 - Turley, Patrick A1 - Chen, Guo-Bo A1 - Emilsson, Valur A1 - Meddens, S Fleur W A1 - Oskarsson, Sven A1 - Pickrell, Joseph K A1 - Thom, Kevin A1 - Pascal N Timshel A1 - de Vlaming, Ronald A1 - Abdel Abdellaoui A1 - Ahluwalia, Tarunveer S A1 - Bacelis, Jonas A1 - Baumbach, Clemens A1 - Bjornsdottir, Gyda A1 - Brandsma, Johannes H A1 - Maria Pina Concas A1 - Derringer, Jaime A1 - Furlotte, Nicholas A A1 - Galesloot, Tessel E A1 - Giorgia G Girotto A1 - Gupta, Richa A1 - Hall, Leanne M A1 - Sarah E Harris A1 - Edith Hofer A1 - Horikoshi, Momoko A1 - Huffman, Jennifer E A1 - Kaasik, Kadri A1 - Ioanna Panagiota Kalafati A1 - Karlsson, Robert A1 - Kong, Augustine A1 - Lahti, Jari A1 - Sven J van der Lee A1 - Christiaan de Leeuw A1 - Penelope A Lind A1 - Lindgren, Karl-Oskar A1 - Tian Liu A1 - Mangino, Massimo A1 - Marten, Jonathan A1 - Mihailov, Evelin A1 - Michael B Miller A1 - van der Most, Peter J A1 - Christopher J Oldmeadow A1 - Payton, Antony A1 - Pervjakova, Natalia A1 - Wouter J Peyrot A1 - Qian, Yong A1 - Olli T Raitakari A1 - Rueedi, Rico A1 - Salvi, Erika A1 - Schmidt, Börge A1 - Schraut, Katharina E A1 - Jianxin Shi A1 - Albert Vernon Smith A1 - Poot, Raymond A A1 - St Pourcain, Beate A1 - Teumer, Alexander A1 - Thorleifsson, Gudmar A1 - Verweij, Niek A1 - Vuckovic, Dragana A1 - Jürgen Wellmann A1 - Westra, Harm-Jan A1 - Yang, Jingyun A1 - Wei Zhao A1 - Zhihong Zhu A1 - Alizadeh, Behrooz Z A1 - Amin, Najaf A1 - Bakshi, Andrew A1 - Baumeister, Sebastian E A1 - Biino, Ginevra A1 - Bønnelykke, Klaus A1 - Patricia A. Boyle A1 - Campbell, Harry A1 - Cappuccio, Francesco P A1 - Gail Davies A1 - De Neve, Jan-Emmanuel A1 - Deloukas, Panos A1 - Demuth, Ilja A1 - Ding, Jun A1 - Eibich, Peter A1 - Eisele, Lewin A1 - Eklund, Niina A1 - Jessica Faul A1 - Feitosa, Mary F A1 - Andreas J Forstner A1 - Gandin, Ilaria A1 - Gunnarsson, Bjarni A1 - Halldórsson, Bjarni V A1 - Tamara B Harris A1 - Andrew C Heath A1 - Lynne J Hocking A1 - Holliday, Elizabeth G A1 - Homuth, Georg A1 - Horan, Michael A A1 - Jouke-Jan Hottenga A1 - Philip L de Jager A1 - Joshi, Peter K A1 - Jugessur, Astanand A1 - Marika A Kaakinen A1 - Kähönen, Mika A1 - Kanoni, Stavroula A1 - Keltigangas-Järvinen, Liisa A1 - Lambertus A Kiemeney A1 - Kolcic, Ivana A1 - Koskinen, Seppo A1 - Kraja, Aldi T A1 - Kroh, Martin A1 - Kutalik, Zoltán A1 - Latvala, Antti A1 - Lenore J Launer A1 - Lebreton, Maël P A1 - Douglas F Levinson A1 - Paul Lichtenstein A1 - Lichtner, Peter A1 - David C Liewald A1 - Loukola, Anu A1 - Pamela A F Madden A1 - Mägi, Reedik A1 - Mäki-Opas, Tomi A1 - Riccardo E Marioni A1 - Marques-Vidal, Pedro A1 - Meddens, Gerardus A A1 - McMahon, George A1 - Meisinger, Christa A1 - Meitinger, Thomas A1 - Milaneschi, Yusplitri A1 - Lili Milani A1 - Grant W Montgomery A1 - Myhre, Ronny A1 - Nelson, Christopher P A1 - Nyholt, Dale R A1 - William E R Ollier A1 - Aarno Palotie A1 - Paternoster, Lavinia A1 - Nancy L Pedersen A1 - Katja E Petrovic A1 - David J Porteous A1 - Katri Räikkönen A1 - Ring, Susan M A1 - Robino, Antonietta A1 - Rostapshova, Olga A1 - Rudan, Igor A1 - Rustichini, Aldo A1 - Veikko Salomaa A1 - Sanders, Alan R A1 - Sarin, Antti-Pekka A1 - Schmidt, Helena A1 - Rodney J Scott A1 - Smith, Blair H A1 - Jennifer A Smith A1 - Staessen, Jan A A1 - Steinhagen-Thiessen, Elisabeth A1 - Strauch, Konstantin A1 - Antonio Terracciano A1 - Tobin, Martin D A1 - Ulivi, Sheila A1 - Vaccargiu, Simona A1 - Quaye, Lydia A1 - van Rooij, Frank J A A1 - Venturini, Cristina A1 - Anna A E Vinkhuyzen A1 - Völker, Uwe A1 - Völzke, Henry A1 - Vonk, Judith M A1 - Vozzi, Diego A1 - Waage, Johannes A1 - Erin B Ware A1 - Gonneke Willemsen A1 - John R. Attia A1 - David A Bennett A1 - Klaus Berger A1 - Bertram, Lars A1 - Bisgaard, Hans A1 - Dorret I Boomsma A1 - Ingrid B Borecki A1 - Bültmann, Ute A1 - Chabris, Christopher F A1 - Francesco Cucca A1 - Cusi, Daniele A1 - Ian J Deary A1 - George Dedoussis A1 - Cornelia M van Duijn A1 - Johan G Eriksson A1 - Franke, Barbara A1 - Lude L Franke A1 - Paolo P. Gasparini A1 - Gejman, Pablo V A1 - Gieger, Christian A1 - Hans-Jörgen Grabe A1 - Gratten, Jacob A1 - Groenen, Patrick J F A1 - Gudnason, Vilmundur A1 - van der Harst, Pim A1 - Caroline Hayward A1 - Hinds, David A A1 - Hoffmann, Wolfgang A1 - Hyppönen, Elina A1 - Iacono, William G A1 - Jacobsson, Bo A1 - Järvelin, Marjo-Riitta A1 - Jöckel, Karl-Heinz A1 - Kaprio, Jaakko A1 - Sharon L R Kardia A1 - Lehtimäki, Terho A1 - Lehrer, Steven F A1 - Patrik K E Magnusson A1 - Nicholas G Martin A1 - McGue, Matt A1 - Andres Metspalu A1 - Pendleton, Neil A1 - Brenda W J H Penninx A1 - Markus Perola A1 - Nicola Pirastu A1 - Pirastu, Mario A1 - Polasek, Ozren A1 - Posthuma, Danielle A1 - Power, Christine A1 - Province, Michael A A1 - Nilesh J Samani A1 - Schlessinger, David A1 - Schmidt, Reinhold A1 - Thorkild I. A. Sørensen A1 - Timothy Spector A1 - Stefansson, Kari A1 - Thorsteinsdottir, Unnur A1 - A. Roy Thurik A1 - Nicholas J Timpson A1 - Henning Tiemeier A1 - Tung, Joyce Y A1 - André G Uitterlinden A1 - Vitart, Veronique A1 - Vollenweider, Peter A1 - David R Weir A1 - James F Wilson A1 - Alan F Wright A1 - Dalton C Conley A1 - Krueger, Robert F A1 - George Davey Smith A1 - Hofman, Albert A1 - David I Laibson A1 - Sarah E Medland A1 - Meyer, Michelle N A1 - Yang, Jian A1 - Johannesson, Magnus A1 - Peter M Visscher A1 - Tõnu Esko A1 - Philipp D Koellinger A1 - Cesarini, David A1 - Daniel J. Benjamin KW - Alzheimer's disease KW - Bipolar Disorder KW - Cognitive Ability KW - Education KW - Fetus KW - Genome-Wide Association Study KW - Humans KW - Molecular Sequence Annotation KW - Polymorphism, Single Nucleotide KW - Schizophrenia KW - United Kingdom AB -

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

VL - 533 IS - 7604 U1 - http://www.ncbi.nlm.nih.gov/pubmed/27225129?dopt=Abstract ER -