@article {11757, title = {Genome-Wide Heritability Estimates for Family Life Course Complexity.}, journal = {Demography}, volume = {58(}, year = {2021}, pages = {1575-1602}, abstract = {

Sequence analysis is an established method used to study the complexity of family life courses. Although individual and societal characteristics have been linked with the complexity of family trajectories, social scientists have neglected the potential role of genetic factors in explaining variation in family transitions and events across the life course. We estimate the genetic contribution to sequence complexity and a wide range of family demographic behaviors using genomic relatedness-based, restricted maximum likelihood models with data from the U.S. Health and Retirement Study. This innovative methodological approach allows us to provide the first estimates of the heritability of composite life course outcomes-that is, sequence complexity. We demonstrate that a number of family demographic indicators (e.g., the age at first birth and first marriage) are heritable and provide evidence that composite metrics can be influenced by genetic factors. For example, our results show that 11\% of the total variation in the complexity of differentiated family sequences is attributable to genetic influences. Moreover, we test whether this genetic contribution varies by social environment as indexed by birth cohort over a period of rapid changes in family norms during the twentieth century. Interestingly, we find evidence that the complexity of fertility and differentiated family trajectories decreased across cohorts, but we find no evidence that the heritability of the complexity of partnership trajectories changed across cohorts. Therefore, our results do not substantiate claims that lower normative constraints on family demographic behavior increase the role of genes.

}, keywords = {biodemography, Family, heritability, life course, Sequence analysis}, issn = {1533-7790}, doi = {10.1215/00703370-9373608}, author = {Van Winkle, Zachary and Dalton C Conley} } @article {11543, title = {The impact of late-career job loss and genetic risk on body mass index: Evidence from variance polygenic scores.}, journal = {Scientific Reports}, volume = {11}, year = {2021}, pages = {7647}, abstract = {

Unemployment shocks from the COVID-19 pandemic have reignited concerns over the long-term effects of job loss on population health. Past research has highlighted the corrosive effects of unemployment on health and health behaviors. This study examines whether the effects of job loss on changes in body mass index (BMI) are moderated by genetic predisposition using data from the U.S. Health and Retirement Study (HRS). To improve detection of gene-by-environment (G {\texttimes} E) interplay, we interacted layoffs from business closures-a plausibly exogenous environmental exposure-with whole-genome polygenic scores (PGSs) that capture genetic contributions to both the population mean (mPGS) and variance (vPGS) of BMI. Results show evidence of genetic moderation using a vPGS (as opposed to an mPGS) and indicate genome-wide summary measures of phenotypic plasticity may further our understanding of how environmental stimuli modify the distribution of complex traits in a population.

}, keywords = {Body Mass Index, Job loss, polygenic score}, issn = {2045-2322}, doi = {10.1038/s41598-021-86716-y}, author = {Lauren L Schmitz and Goodwin, Julia and Miao, Jiacheng and Lu, Qiongshi and Dalton C Conley} } @article {10712, title = {Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals.}, journal = {Nature Genetics}, volume = {50}, year = {2018}, month = {2018 07 23}, pages = {1112-1121}, abstract = {

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.

}, keywords = {Adult, Aged, Aged, 80 and over, Cohort Studies, Educational Status, Female, Genome-Wide Association Study, Humans, Male, Middle Aged, Multifactorial Inheritance, Phenotype, Polymorphism, Single Nucleotide}, issn = {1546-1718}, doi = {10.1038/s41588-018-0147-3}, author = {Lee, James J and Wedow, Robbee and Okbay, Aysu and Kong, Edward and Maghzian, Omeed and Zacher, Meghan and Nguyen-Viet, Tuan Anh and Bowers, Peter and Sidorenko, Julia and Richard Karlsson Linn{\'e}r and Mark Alan Fontana and Kundu, Tushar and Lee, Chanwook and Hui Liu and Li, Ruoxi and Royer, Rebecca and Pascal N Timshel and Walters, Raymond K and Willoughby, Emily A and Yengo, Loic and Alver, Maris and Bao, Yanchun and Clark, David W and Day, Felix R and Furlotte, Nicholas A and Joshi, Peter K and Kathryn E Kemper and Kleinman, Aaron and Langenberg, Claudia and M{\"a}gi, Reedik and Joey W Trampush and Verma, Shefali Setia and Wu, Yang and Lam, Max and Jing Hua Zhao and Zheng, Zhili and Jason D Boardman and Campbell, Harry and Freese, Jeremy and Kathleen Mullan Harris and Caroline Hayward and Herd, Pamela and Kumari, Meena and Lencz, Todd and Luan, Jian{\textquoteright}an and Anil K. Malhotra and Andres Metspalu and Lili Milani and Ong, Ken K and Perry, John R B and David J Porteous and Ritchie, Marylyn D and Smart, Melissa C and Smith, Blair H and Tung, Joyce Y and Wareham, Nicholas J and James F Wilson and Jonathan P. Beauchamp and Dalton C Conley and T{\~o}nu Esko and Lehrer, Steven F and Patrik K E Magnusson and Oskarsson, Sven and Pers, Tune H and Matthew R Robinson and Thom, Kevin and Watson, Chelsea and Chabris, Christopher F and Meyer, Michelle N and David I Laibson and Yang, Jian and Johannesson, Magnus and Philipp D Koellinger and Turley, Patrick and Peter M Visscher and Daniel J. Benjamin and Cesarini, David} } @article {9514, title = {The Effect of Vietnam-Era Conscription and Genetic Potential for Educational Attainment on Schooling Outcomes.}, journal = {Economics of Education Review}, volume = {61}, year = {2017}, pages = {85-97}, abstract = {This study examines whether draft lottery estimates of the causal effects of Vietnam-era military service on schooling vary by an individual{\textquoteright}s genetic propensity toward educational attainment. To capture the complex genetic architecture that underlies the bio-developmental pathways, behavioral traits and evoked environments associated with educational attainment, we construct polygenic scores (PGS) for respondents in the Health and Retirement Study (HRS) that aggregate thousands of individual loci across the human genome and weight them by effect sizes derived from a recent genome-wide association study (GWAS) of years of education. Our findings suggest veterans with below average PGSs for educational attainment may have completed fewer years of schooling than comparable non-veterans. On the other hand, we do not find any difference in the educational attainment of veterans and non-veterans with above average PGSs. Results indicate that public policies and exogenous environments may induce heterogeneous treatment effects by genetic disposition.}, keywords = {Education, Genetics, GWAS, PGS, Veterans}, issn = {0272-7757}, doi = {10.1016/j.econedurev.2017.10.001}, author = {Lauren L Schmitz and Dalton C Conley} } @article {9049, title = {Mortality selection in a genetic sample and implications for association studies.}, journal = {International Journal of Epidemiolpgy}, volume = {46}, year = {2017}, month = {08/2017}, abstract = {

Background: Mortality selection occurs when a non-random subset of a population of interest has died before data collection and is unobserved in the data. Mortality selection is of general concern in the social and health sciences, but has received little attention in genetic epidemiology. We tested the hypothesis that mortality selection may bias genetic association estimates, using data from the US-based Health and Retirement Study (HRS).

Methods: We tested mortality selection into the HRS genetic database by comparing HRS respondents who survive until genetic data collection in 2006 with those who do not. We next modelled mortality selection on demographic, health and social characteristics to calculate mortality selection probability weights. We analysed polygenic score associations with several traits before and after applying inverse-probability weighting to account for mortality selection. We tested simple associations and time-varying genetic associations (i.e. gene-by-cohort interactions).

Results: We observed mortality selection into the HRS genetic database on demographic, health and social characteristics. Correction for mortality selection using inverse probability weighting methods did not change simple association estimates. However, using these methods did change estimates of gene-by-cohort interaction effects. Correction for mortality selection changed gene-by-cohort interaction estimates in the opposite direction from increased mortality selection based on analysis of HRS respondents surviving through 2012.

Conclusions: Mortality selection may bias estimates of gene-by-cohort interaction effects. Analyses of HRS data can adjust for mortality selection associated with observables by including probability weights. Mortality selection is a potential confounder of genetic association studies, but the magnitude of confounding varies by trait.

}, keywords = {Genetics, GWAS, Mortality}, issn = {1464-3685}, doi = {10.1093/ije/dyx041}, author = {Benjamin W Domingue and Daniel W. Belsky and Harrati, Amal and Dalton C Conley and David R Weir and Jason D Boardman} } @article {8389, title = {Cohort Effects in the Genetic Influence on Smoking.}, journal = {Behav Genet}, volume = {46}, year = {2016}, note = {Export Date: 9 September 2015 Article in Press}, month = {2016 Jan}, pages = {31-42}, publisher = {46}, abstract = {

We examine the hypothesis that the heritability of smoking has varied over the course of recent history as a function of associated changes in the composition of the smoking and non-smoking populations. Classical twin-based heritability analysis has suggested that genetic basis of smoking has increased as the information about the harms of tobacco has become more prevalent-particularly after the issuance of the 1964 Surgeon General{\textquoteright}s Report. In the present paper we deploy alternative methods to test this claim. We use data from the Health and Retirement Study to estimate cohort differences in the genetic influence on smoking using both genomic-relatedness-matrix restricted maximum likelihood and a modified DeFries-Fulker approach. We perform a similar exercise deploying a polygenic score for smoking using results generated by the Tobacco and Genetics consortium. The results support earlier claims that the genetic influence in smoking behavior has increased over time. Emphasizing historical periods and birth cohorts as environmental factors has benefits over existing GxE research. Our results provide additional support for the idea that anti-smoking policies of the 1980s may not be as effective because of the increasingly important role of genotype as a determinant of smoking status.

}, keywords = {Aged, Cohort Effect, Female, Gene Frequency, Genetic Predisposition to Disease, Genotype, Humans, Male, Middle Aged, Multifactorial Inheritance, Smoking, Twins}, issn = {1573-3297}, doi = {10.1007/s10519-015-9731-9}, url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84938496073andpartnerID=40andmd5=76a4f2cefad88fc22ebca2e435b4323e}, author = {Benjamin W Domingue and Dalton C Conley and Jason M. Fletcher and Jason D Boardman} } @article {8618, title = {Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses.}, journal = {Nat Genet}, volume = {48}, year = {2016}, month = {2016 06}, pages = {624-33}, abstract = {

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

}, keywords = {Anxiety Disorders, Bayes Theorem, depression, Genome-Wide Association Study, Humans, Neuroticism, Phenotype, Polymorphism, Single Nucleotide}, issn = {1546-1718}, doi = {10.1038/ng.3552}, author = {Okbay, Aysu and Baselmans, Bart M L and De Neve, Jan-Emmanuel and Turley, Patrick and Nivard, Michel G and Mark Alan Fontana and Meddens, S Fleur W and Richard Karlsson Linn{\'e}r and Cornelius A Rietveld and Derringer, Jaime and Gratten, Jacob and Lee, James J and Liu, Jimmy Z and de Vlaming, Ronald and Ahluwalia, Tarunveer S and Buchwald, Jadwiga and Cavadino, Alana and Frazier-Wood, Alexis C and Furlotte, Nicholas A and Garfield, Victoria and Geisel, Marie Henrike and Gonzalez, Juan R and Haitjema, Saskia and Karlsson, Robert and van der Laan, Sander W and Ladwig, Karl-Heinz and J. Lahti and Sven J van der Lee and Penelope A Lind and Tian Liu and Lindsay K Matteson and Mihailov, Evelin and Michael B Miller and Minica, Camelia C and Ilja M Nolte and Dennis O Mook-Kanamori and van der Most, Peter J and Christopher J Oldmeadow and Qian, Yong and Olli T Raitakari and Rawal, Rajesh and Realo, Anu and Rueedi, Rico and Schmidt, B{\"o}rge and Albert Vernon Smith and Stergiakouli, Evie and Toshiko Tanaka and Kent D Taylor and Wedenoja, Juho and J{\"u}rgen Wellmann and Westra, Harm-Jan and Willems, Sara M and Wei Zhao and Amin, Najaf and Bakshi, Andrew and Patricia A. Boyle and Cherney, Samantha and Cox, Simon R and Gail Davies and Davis, Oliver S P and Ding, Jun and Nese Direk and Eibich, Peter and Emeny, Rebecca T and Fatemifar, Ghazaleh and Jessica Faul and Luigi Ferrucci and Andreas J Forstner and Gieger, Christian and Gupta, Richa and Tamara B Harris and Harris, Juliette M and Holliday, Elizabeth G and Jouke-Jan Hottenga and Philip L de Jager and Marika A Kaakinen and Kajantie, Eero and Karhunen, Ville and Kolcic, Ivana and Kumari, Meena and Lenore J Launer and Lude L Franke and Li-Gao, Ruifang and Koini, Marisa and Loukola, Anu and Marques-Vidal, Pedro and Grant W Montgomery and Mosing, Miriam A and Paternoster, Lavinia and Pattie, Alison and Katja E Petrovic and Pulkki-Raback, Laura and Quaye, Lydia and Katri R{\"a}ikk{\"o}nen and Rudan, Igor and Rodney J Scott and Jennifer A Smith and Angelina R Sutin and Trzaskowski, Maciej and Anna A E Vinkhuyzen and Lei Yu and Zabaneh, Delilah and John R. Attia and David A Bennett and Klaus Berger and Bertram, Lars and Dorret I Boomsma and Snieder, Harold and Chang, Shun-Chiao and Francesco Cucca and Ian J Deary and Cornelia M van Duijn and Johan G Eriksson and B{\"u}ltmann, Ute and Eco J. C. de Geus and Groenen, Patrick J F and Gudnason, Vilmundur and Hansen, Torben and Catharina A Hartman and Haworth, Claire M A and Caroline Hayward and Andrew C Heath and Hinds, David A and Hypp{\"o}nen, Elina and Iacono, William G and J{\"a}rvelin, Marjo-Riitta and J{\"o}ckel, Karl-Heinz and Kaprio, Jaakko and Sharon L R Kardia and Keltikangas-J{\"a}rvinen, Liisa and Kraft, Peter and Laura D Kubzansky and Lehtim{\"a}ki, Terho and Patrik K E Magnusson and Nicholas G Martin and McGue, Matt and Andres Metspalu and Melinda C Mills and de Mutsert, Ren{\'e}e and Oldehinkel, Albertine J and Pasterkamp, Gerard and Nancy L Pedersen and Plomin, Robert and Polasek, Ozren and Power, Christine and Rich, Stephen S and Rosendaal, Frits R and Hester M. den Ruijter and Schlessinger, David and Schmidt, Helena and Svento, Rauli and Schmidt, Reinhold and Alizadeh, Behrooz Z and Thorkild I. A. S{\o}rensen and Timothy Spector and Andrew Steptoe and Antonio Terracciano and A. Roy Thurik and Nicholas J Timpson and Henning Tiemeier and Andr{\'e} G Uitterlinden and Vollenweider, Peter and Wagner, Gert G and David R Weir and Yang, Jian and Dalton C Conley and Hofman, Albert and Johannesson, Magnus and David I Laibson and Sarah E Medland and Meyer, Michelle N and Pickrell, Joseph K and T{\~o}nu Esko and Krueger, Robert F and Jonathan P. Beauchamp and Philipp D Koellinger and Daniel J. Benjamin and Bartels, Meike and Cesarini, David} } @article {8883, title = {Genome-wide association study identifies 74 loci associated with educational attainment.}, journal = {Nature}, volume = {533}, year = {2016}, month = {2016 05 26}, pages = {539-42}, abstract = {

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

}, keywords = {Alzheimer{\textquoteright}s disease, Bipolar Disorder, Cognitive Ability, Education, Fetus, Genome-Wide Association Study, Humans, Molecular Sequence Annotation, Polymorphism, Single Nucleotide, Schizophrenia, United Kingdom}, issn = {1476-4687}, doi = {10.1038/nature17671}, author = {Okbay, Aysu and Jonathan P. Beauchamp and Mark Alan Fontana and Lee, James J and Pers, Tune H and Cornelius A Rietveld and Turley, Patrick and Chen, Guo-Bo and Emilsson, Valur and Meddens, S Fleur W and Oskarsson, Sven and Pickrell, Joseph K and Thom, Kevin and Pascal N Timshel and de Vlaming, Ronald and Abdel Abdellaoui and Ahluwalia, Tarunveer S and Bacelis, Jonas and Baumbach, Clemens and Bjornsdottir, Gyda and Brandsma, Johannes H and Maria Pina Concas and Derringer, Jaime and Furlotte, Nicholas A and Galesloot, Tessel E and Giorgia G Girotto and Gupta, Richa and Hall, Leanne M and Sarah E Harris and Edith Hofer and Horikoshi, Momoko and Huffman, Jennifer E and Kaasik, Kadri and Ioanna Panagiota Kalafati and Karlsson, Robert and Kong, Augustine and Lahti, Jari and Sven J van der Lee and Christiaan de Leeuw and Penelope A Lind and Lindgren, Karl-Oskar and Tian Liu and Mangino, Massimo and Marten, Jonathan and Mihailov, Evelin and Michael B Miller and van der Most, Peter J and Christopher J Oldmeadow and Payton, Antony and Pervjakova, Natalia and Wouter J Peyrot and Qian, Yong and Olli T Raitakari and Rueedi, Rico and Salvi, Erika and Schmidt, B{\"o}rge and Schraut, Katharina E and Jianxin Shi and Albert Vernon Smith and Poot, Raymond A and St Pourcain, Beate and Teumer, Alexander and Thorleifsson, Gudmar and Verweij, Niek and Vuckovic, Dragana and J{\"u}rgen Wellmann and Westra, Harm-Jan and Yang, Jingyun and Wei Zhao and Zhihong Zhu and Alizadeh, Behrooz Z and Amin, Najaf and Bakshi, Andrew and Baumeister, Sebastian E and Biino, Ginevra and B{\o}nnelykke, Klaus and Patricia A. Boyle and Campbell, Harry and Cappuccio, Francesco P and Gail Davies and De Neve, Jan-Emmanuel and Deloukas, Panos and Demuth, Ilja and Ding, Jun and Eibich, Peter and Eisele, Lewin and Eklund, Niina and Jessica Faul and Feitosa, Mary F and Andreas J Forstner and Gandin, Ilaria and Gunnarsson, Bjarni and Halld{\'o}rsson, Bjarni V and Tamara B Harris and Andrew C Heath and Lynne J Hocking and Holliday, Elizabeth G and Homuth, Georg and Horan, Michael A and Jouke-Jan Hottenga and Philip L de Jager and Joshi, Peter K and Jugessur, Astanand and Marika A Kaakinen and K{\"a}h{\"o}nen, Mika and Kanoni, Stavroula and Keltigangas-J{\"a}rvinen, Liisa and Lambertus A Kiemeney and Kolcic, Ivana and Koskinen, Seppo and Kraja, Aldi T and Kroh, Martin and Kutalik, Zolt{\'a}n and Latvala, Antti and Lenore J Launer and Lebreton, Ma{\"e}l P and Douglas F Levinson and Paul Lichtenstein and Lichtner, Peter and David C Liewald and Loukola, Anu and Pamela A F Madden and M{\"a}gi, Reedik and M{\"a}ki-Opas, Tomi and Riccardo E Marioni and Marques-Vidal, Pedro and Meddens, Gerardus A and McMahon, George and Meisinger, Christa and Meitinger, Thomas and Milaneschi, Yusplitri and Lili Milani and Grant W Montgomery and Myhre, Ronny and Nelson, Christopher P and Nyholt, Dale R and William E R Ollier and Aarno Palotie and Paternoster, Lavinia and Nancy L Pedersen and Katja E Petrovic and David J Porteous and Katri R{\"a}ikk{\"o}nen and Ring, Susan M and Robino, Antonietta and Rostapshova, Olga and Rudan, Igor and Rustichini, Aldo and Veikko Salomaa and Sanders, Alan R and Sarin, Antti-Pekka and Schmidt, Helena and Rodney J Scott and Smith, Blair H and Jennifer A Smith and Staessen, Jan A and Steinhagen-Thiessen, Elisabeth and Strauch, Konstantin and Antonio Terracciano and Tobin, Martin D and Ulivi, Sheila and Vaccargiu, Simona and Quaye, Lydia and van Rooij, Frank J A and Venturini, Cristina and Anna A E Vinkhuyzen and V{\"o}lker, Uwe and V{\"o}lzke, Henry and Vonk, Judith M and Vozzi, Diego and Waage, Johannes and Erin B Ware and Gonneke Willemsen and John R. Attia and David A Bennett and Klaus Berger and Bertram, Lars and Bisgaard, Hans and Dorret I Boomsma and Ingrid B Borecki and B{\"u}ltmann, Ute and Chabris, Christopher F and Francesco Cucca and Cusi, Daniele and Ian J Deary and George Dedoussis and Cornelia M van Duijn and Johan G Eriksson and Franke, Barbara and Lude L Franke and Paolo P. Gasparini and Gejman, Pablo V and Gieger, Christian and Hans-J{\"o}rgen Grabe and Gratten, Jacob and Groenen, Patrick J F and Gudnason, Vilmundur and van der Harst, Pim and Caroline Hayward and Hinds, David A and Hoffmann, Wolfgang and Hypp{\"o}nen, Elina and Iacono, William G and Jacobsson, Bo and J{\"a}rvelin, Marjo-Riitta and J{\"o}ckel, Karl-Heinz and Kaprio, Jaakko and Sharon L R Kardia and Lehtim{\"a}ki, Terho and Lehrer, Steven F and Patrik K E Magnusson and Nicholas G Martin and McGue, Matt and Andres Metspalu and Pendleton, Neil and Brenda W J H Penninx and Markus Perola and Nicola Pirastu and Pirastu, Mario and Polasek, Ozren and Posthuma, Danielle and Power, Christine and Province, Michael A and Nilesh J Samani and Schlessinger, David and Schmidt, Reinhold and Thorkild I. A. S{\o}rensen and Timothy Spector and Stefansson, Kari and Thorsteinsdottir, Unnur and A. Roy Thurik and Nicholas J Timpson and Henning Tiemeier and Tung, Joyce Y and Andr{\'e} G Uitterlinden and Vitart, Veronique and Vollenweider, Peter and David R Weir and James F Wilson and Alan F Wright and Dalton C Conley and Krueger, Robert F and George Davey Smith and Hofman, Albert and David I Laibson and Sarah E Medland and Meyer, Michelle N and Yang, Jian and Johannesson, Magnus and Peter M Visscher and T{\~o}nu Esko and Philipp D Koellinger and Cesarini, David and Daniel J. Benjamin} } @article {8543, title = {The Impact of Late-Career Job Loss and Genotype on Body Mass Index}, number = {Working Paper 22348}, year = {2016}, month = {06/2016}, pages = {1-44}, institution = {National Bureau of Economic Research}, address = {Cambridge, MA}, abstract = {This study examines whether the effect of job loss on body mass index (BMI) at older ages is moderated by genotype using twenty years of socio-demographic and genome-wide data from the Health and Retirement Study (HRS). To avoid any potential confounding we interact layoffs due to a plant or business closure{\textemdash}a plausibly exogenous environmental exposure{\textemdash}with a polygenic risk score for BMI in a regression-adjusted semiparametric differences-in-differences matching framework that compares the BMI of those before and after an involuntary job loss with a control group that has not been laid off. Results indicate genetically-at-risk workers who lost their job before they were eligible for Social Security benefits, or before age 62, were more likely to gain weight. Further analysis reveals heterogeneous treatment effects by demographic, health, and socioeconomic characteristics. In particular, we find high risk individuals who gained weight after a job loss were more likely to be male, in worse health, single, and at the bottom half of the wealth distribution. Across the board, effects are concentrated among high-risk individuals who were not overweight prior to job loss, indicating unemployment at older ages may trigger weight gain in otherwise healthy or normal weight populations. }, keywords = {BMI, Genome, Job loss, Older Adults}, doi = {10.3386/w22348}, url = {http://www.nber.org/papers/w22348.pdf}, author = {Lauren L Schmitz and Dalton C Conley} } @article {8621, title = {The Long-Term Consequences of Vietnam-Era Conscription and Genotype on Smoking Behavior and Health.}, journal = {Behav Genet}, volume = {46}, year = {2016}, month = {2016 Jan}, pages = {43-58}, abstract = {

Research is needed to understand the extent to which environmental factors moderate links between genetic risk and the development of smoking behaviors. The Vietnam-era draft lottery offers a unique opportunity to investigate whether genetic susceptibility to smoking is influenced by risky environments in young adulthood. Access to free or reduced-price cigarettes coupled with the stress of military life meant conscripts were exposed to a large, exogenous shock to smoking behavior at a young age. Using data from the Health and Retirement Study (HRS), we interact a genetic risk score for smoking initiation with instrumented veteran status in an instrumental variables (IV) framework to test for genetic moderation (i.e. heterogeneous treatment effects) of veteran status on smoking behavior and smoking-related morbidities. We find evidence that veterans with a high genetic predisposition for smoking were more likely to have been smokers, smoke heavily, and are at a higher risk of being diagnosed with cancer or hypertension at older ages. Smoking behavior was significantly attenuated for high-risk veterans who attended college after the war, indicating post-service schooling gains from veterans{\textquoteright} use of the GI Bill may have reduced tobacco consumption in adulthood.

}, keywords = {Adult, Aged, Female, Gene-Environment Interaction, Genetic Predisposition to Disease, Genotype, Humans, Male, Middle Aged, Risk Factors, Smoking, Tobacco Use Disorder, Veterans, Vietnam Conflict}, issn = {1573-3297}, doi = {10.1007/s10519-015-9739-1}, author = {Lauren L Schmitz and Dalton C Conley} } @article {5865, title = {The Long-Term Consequences of Vietnam-Era Conscription and Genotype on Smoking Behavior and Health}, year = {2015}, abstract = {Research is needed to understand the extent to which environmental factors mediate links between genetic risk and the development of smoking behaviors. The Vietnam-era draft lottery offers a unique opportunity to investigate whether genetic susceptibility to smoking is influenced by risky environments in young adulthood. Access to free or reduced-price cigarettes coupled with the stress of military life meant conscripts were exposed to a large, exogenous shock to smoking behavior at a young age. Using data from the Health and Retirement Study (HRS), we interact a genetic risk score for smoking initiation with instrumented veteran status in an instrumental variables (IV) framework to test for genetic moderation (i.e. heterogeneous treatment effects) of veteran status on smoking behavior and smoking-related morbidities. We find evidence that veterans with a high genetic predisposition for smoking were more likely to become regular smokers, smoke heavily, and are at a higher risk of being diagnosed with cancer or hypertension at older ages. Smoking behavior was significantly attenuated for high-risk veterans who attended college after the war, indicating post-service schooling gains from veterans{\textquoteright} use of the GI Bill may have reduced tobacco consumption in adulthood.}, keywords = {Demographics, Health Conditions and Status}, author = {Lauren L Schmitz and Dalton C Conley} } @article {10656, title = {Common genetic variants associated with cognitive performance identified using the proxy-phenotype method.}, journal = {Proc Natl Acad Sci U S A}, volume = {111}, year = {2014}, month = {2014 Sep 23}, pages = {13790-4}, abstract = {

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

}, keywords = {Cell Adhesion Molecules, Neuronal, Cognition, Female, Humans, Learning, Male, Memory, Multifactorial Inheritance, Nerve Tissue Proteins, Neuronal Plasticity, Octamer Transcription Factors, Polymorphism, Single Nucleotide, Synaptic Transmission}, issn = {1091-6490}, doi = {10.1073/pnas.1404623111}, author = {Cornelius A Rietveld and T{\~o}nu Esko and Gail Davies and Pers, Tune H and Turley, Patrick and Benyamin, Beben and Chabris, Christopher F and Emilsson, Valur and Andrew D Johnson and Lee, James J and Christiaan de Leeuw and Riccardo E Marioni and Sarah E Medland and Michael B Miller and Rostapshova, Olga and Sven J van der Lee and Anna A E Vinkhuyzen and Amin, Najaf and Dalton C Conley and Derringer, Jaime and Cornelia M van Duijn and Fehrmann, Rudolf and Lude L Franke and Edward L Glaeser and Narelle K Hansell and Caroline Hayward and Iacono, William G and Carla A Ibrahim-Verbaas and Vincent Jaddoe and Karjalainen, Juha and David I Laibson and Paul Lichtenstein and David C Liewald and Patrik K E Magnusson and Nicholas G Martin and McGue, Matt and McMahon, George and Nancy L Pedersen and Pinker, Steven and David J Porteous and Posthuma, Danielle and Fernando Rivadeneira and Smith, Blair H and John M Starr and Henning Tiemeier and Nicholas J Timpson and Trzaskowski, Maciej and Andr{\'e} G Uitterlinden and Verhulst, Frank C and Mary E Ward and Margaret J Wright and George Davey Smith and Ian J Deary and Johannesson, Magnus and Plomin, Robert and Peter M Visscher and Daniel J. Benjamin and Cesarini, David and Philipp D Koellinger} } @article {8110, title = {Genetic and educational assortative mating among US adults.}, journal = {Proc Natl Acad Sci U S A}, volume = {111}, year = {2014}, note = {Times Cited: 0}, month = {2014 Jun 03}, pages = {7996-8000}, publisher = {111}, abstract = {

Understanding the social and biological mechanisms that lead to homogamy (similar individuals marrying one another) has been a long-standing issue across many fields of scientific inquiry. Using a nationally representative sample of non-Hispanic white US adults from the Health and Retirement Study and information from 1.7 million single-nucleotide polymorphisms, we compare genetic similarity among married couples to noncoupled pairs in the population. We provide evidence for genetic assortative mating in this population but the strength of this association is substantially smaller than the strength of educational assortative mating in the same sample. Furthermore, genetic similarity explains at most 10\% of the assortative mating by education levels. Results are replicated using comparable data from the Framingham Heart Study.

}, keywords = {Databases, Genetic, Educational Status, ethnicity, Female, Genome-Wide Association Study, Genotype, Humans, Male, Marriage, Metagenomics, Phenotype, Racial Groups, Sexual Behavior, Spouses, United States}, issn = {1091-6490}, doi = {10.1073/pnas.1321426111}, author = {Benjamin W Domingue and Jason M. Fletcher and Dalton C Conley and Jason D Boardman} } @article {7993, title = {Testing the key assumption of heritability estimates based on genome-wide genetic relatedness.}, journal = {J Hum Genet}, volume = {59}, year = {2014}, month = {2014 Jun}, pages = {342-5}, publisher = {59}, abstract = {

Comparing genetic and phenotypic similarity among unrelated individuals seems a promising way to quantify the genetic component of traits while avoiding the problematic assumptions plaguing twin- and other kin-based estimates of heritability. One approach uses a Genetic Relatedness Estimation through Maximum Likelihood (GREML) model for individuals who are related at less than 0.025 to predict their phenotypic similarity by their genetic similarity. Here we test the key underlying assumption of this approach: that genetic relatedness is orthogonal to environmental similarity. Using data from the Health and Retirement Study (and two other surveys), we show two unrelated individuals may be more likely to have been reared in a similar environment (urban versus nonurban setting) if they are genetically similar. This effect is not eliminated by controls for population structure. However, when we include this environmental confound in GREML models, heritabilities do not change substantially and thus potential bias in estimates of most biological phenotypes is probably minimal.

}, keywords = {Body Height, Body Weight, Educational Status, Gene-Environment Interaction, Genome, Human, Humans, Likelihood Functions, Models, Genetic, Phenotype, Quantitative Trait, Heritable, Urban Population}, issn = {1435-232X}, doi = {10.1038/jhg.2014.14}, author = {Dalton C Conley and Mark L Siegal and Benjamin W Domingue and Kathleen Mullan Harris and Matthew B McQueen and Jason D Boardman} } @article {8620, title = {GWAS of 126,559 individuals identifies genetic variants associated with educational attainment.}, journal = {Science}, volume = {340}, year = {2013}, month = {2013 Jun 21}, pages = {1467-71}, abstract = {

A genome-wide association study (GWAS) of educational attainment was conducted in a discovery sample of 101,069 individuals and a replication sample of 25,490. Three independent single-nucleotide polymorphisms (SNPs) are genome-wide significant (rs9320913, rs11584700, rs4851266), and all three replicate. Estimated effects sizes are small (coefficient of determination R(2) ≈ 0.02\%), approximately 1 month of schooling per allele. A linear polygenic score from all measured SNPs accounts for ≈2\% of the variance in both educational attainment and cognitive function. Genes in the region of the loci have previously been associated with health, cognitive, and central nervous system phenotypes, and bioinformatics analyses suggest the involvement of the anterior caudate nucleus. These findings provide promising candidate SNPs for follow-up work, and our effect size estimates can anchor power analyses in social-science genetics.

}, keywords = {Cognition, Educational Status, Endophenotypes, Female, Genetic Loci, Genome-Wide Association Study, Humans, Male, Multifactorial Inheritance, Polymorphism, Single Nucleotide}, issn = {1095-9203}, doi = {10.1126/science.1235488}, author = {Cornelius A Rietveld and Sarah E Medland and Derringer, Jaime and Yang, Jian and T{\~o}nu Esko and Martin, Nicolas W and Westra, Harm-Jan and Shakhbazov, Konstantin and Abdel Abdellaoui and Agrawal, Arpana and Albrecht, Eva and Alizadeh, Behrooz Z and Amin, Najaf and Barnard, John and Baumeister, Sebastian E and Benke, Kelly S and Bielak, Lawrence F and Boatman, Jeffrey A and Patricia A. Boyle and Gail Davies and Christiaan de Leeuw and Eklund, Niina and Daniel S Evans and Rudolf Ferhmann and Fischer, Krista and Gieger, Christian and Gjessing, H{\r a}kon K and H{\"a}gg, Sara and Harris, Jennifer R and Caroline Hayward and Holzapfel, Christina and Carla A Ibrahim-Verbaas and Ingelsson, Erik and Jacobsson, Bo and Joshi, Peter K and Jugessur, Astanand and Marika A Kaakinen and Kanoni, Stavroula and Karjalainen, Juha and Kolcic, Ivana and Kristiansson, Kati and Kutalik, Zolt{\'a}n and J. Lahti and Lee, Sang H and Lin, Peng and Penelope A Lind and Yongmei Liu and Kurt Lohman and Loitfelder, Marisa and McMahon, George and Vidal, Pedro Marques and Osorio Meirelles and Lili Milani and Myhre, Ronny and Nuotio, Marja-Liisa and Christopher J Oldmeadow and Katja E Petrovic and Wouter J Peyrot and Polasek, Ozren and Quaye, Lydia and Reinmaa, Eva and Rice, John P and Rizzi, Thais S and Schmidt, Helena and Schmidt, Reinhold and Albert Vernon Smith and Jennifer A Smith and Toshiko Tanaka and Antonio Terracciano and van der Loos, Matthijs J H M and Vitart, Veronique and V{\"o}lzke, Henry and J{\"u}rgen Wellmann and Lei Yu and Wei Zhao and Allik, J{\"u}ri and John R. Attia and Bandinelli, Stefania and Bastardot, Fran{\c c}ois and Jonathan P. Beauchamp and David A Bennett and Klaus Berger and Laura Bierut and Dorret I Boomsma and B{\"u}ltmann, Ute and Campbell, Harry and Chabris, Christopher F and Cherkas, Lynn and Chung, Mina K and Francesco Cucca and de Andrade, Mariza and Philip L de Jager and De Neve, Jan-Emmanuel and Ian J Deary and George Dedoussis and Deloukas, Panos and Dimitriou, Maria and Gu{\dh}ny Eir{\'\i}ksd{\'o}ttir and Elderson, Martin F and Johan G Eriksson and Jessica Faul and Luigi Ferrucci and Melissa E Garcia and Gr{\"o}nberg, Henrik and Gu{\dh}nason, Vilmundur and Hall, Per and Harris, Juliette M and Tamara B Harris and Nicholas D Hastie and Andrew C Heath and Dena G Hernandez and Hoffmann, Wolfgang and Hofman, Adriaan and Holle, Rolf and Holliday, Elizabeth G and Jouke-Jan Hottenga and Iacono, William G and Illig, Thomas and J{\"a}rvelin, Marjo-Riitta and K{\"a}h{\"o}nen, Mika and Kaprio, Jaakko and Kirkpatrick, Robert M and Kowgier, Matthew and Latvala, Antti and Lenore J Launer and Lawlor, Debbie A and Lehtim{\"a}ki, Terho and Li, Jingmei and Paul Lichtenstein and Lichtner, Peter and David C Liewald and Pamela A F Madden and Patrik K E Magnusson and M{\"a}kinen, Tomi E and Masala, Marco and McGue, Matt and Andres Metspalu and Mielck, Andreas and Michael B Miller and Grant W Montgomery and Mukherjee, Sutapa and Nyholt, Dale R and Ben A Oostra and Palmer, Lyle J and Aarno Palotie and Brenda W J H Penninx and Markus Perola and Peyser, Patricia A and Preisig, Martin and Katri R{\"a}ikk{\"o}nen and Olli T Raitakari and Realo, Anu and Ring, Susan M and Ripatti, Samuli and Fernando Rivadeneira and Rudan, Igor and Rustichini, Aldo and Veikko Salomaa and Sarin, Antti-Pekka and Schlessinger, David and Rodney J Scott and Snieder, Harold and St Pourcain, Beate and John M Starr and Sul, Jae Hoon and Surakka, Ida and Svento, Rauli and Teumer, Alexander and Henning Tiemeier and van Rooij, Frank J A and Van Wagoner, David R and Vartiainen, Erkki and Viikari, Jorma and Vollenweider, Peter and Vonk, Judith M and Waeber, G{\'e}rard and David R Weir and Wichmann, H-Erich and Elisabeth Widen and Gonneke Willemsen and James F Wilson and Alan F Wright and Dalton C Conley and Davey-Smith, George and Lude L Franke and Groenen, Patrick J F and Hofman, Albert and Johannesson, Magnus and Sharon L R Kardia and Krueger, Robert F and David I Laibson and Nicholas G Martin and Meyer, Michelle N and Posthuma, Danielle and A. Roy Thurik and Nicholas J Timpson and Andr{\'e} G Uitterlinden and Cornelia M van Duijn and Peter M Visscher and Daniel J. Benjamin and Cesarini, David and Philipp D Koellinger} }