TY - JOUR T1 - Educational attainment and allostatic load in later life: Evidence using genetic markers JF - Preventive Medicine Y1 - 2019 A1 - Ding, Xuejie A1 - Nicola Barban A1 - Melinda C Mills KW - Allostatic load KW - Instrumental variable KW - Mendelian randomization KW - Polygenic risk score KW - Years of education AB - Education is strongly correlated with health outcomes in older adulthood. Whether the impact of education expansion improves health remains unclear due to a lack of clarity over the causal relationship. Previous health research within the social sciences has tended to use specific activities of daily living or self-reported health status. This study uses a broader and objective health measure - allostatic load (AL) - to take into consideration the exposures that accumulate throughout the life course. This paper applies a Mendelian Randomization (MR) approach to identify causality in relation to education on health as measured by AL. Using the Health and Retirement Study 2008 (N = 3935), we adopt a polygenic score built from genetic variants associated with years of education. To test whether our analyses violate the exclusion assumption, we further run MR Egger regressions to test for bias from pleiotropy. We also explore the potential pathways between education and AL, including smoking, drinking, marital length, health insurance, etc. Using this genetic instrument, we find a 0.3 unit (19% of a standard deviation) reduction in AL per year of schooling. The effect is mainly driven by BMI and Hba1c. Smoking and marital stability are two potential pathways that also causally influenced by education. If our main and sensitivity analyses are valid, the results find support that a higher level of education is causally related to better health in older adulthood. VL - 129 ER - TY - JOUR T1 - The relationship between cognitive decline and a genetic predictor of educational attainment. JF - Soc Sci Med Y1 - 2019 A1 - Ding, Xuejie A1 - Nicola Barban A1 - Felix C Tropf A1 - Melinda C Mills KW - Cognitive decline KW - Educational attainment KW - Fluid/crystallised intelligence KW - Genetic predictor KW - Growth curve modelling KW - Polygenic risk score AB -

Genetic and environmental factors both make substantial contributions to the heterogeneity in individuals' levels of cognitive ability. Many studies have examined the relationship between educational attainment and cognitive performance and its rate of change. Yet there remains a gap in knowledge regarding whether the effect of genetic predictors on individual differences in cognition becomes more or less prominent over the life course. In this analysis of over 5000 older adults from the Health and Retirement Study (HRS) in the U.S., we measured the change in performance on global cognition, episodic memory, attention & concentration, and mental status over 14 years. Growth curve models are used to evaluate the association between a polygenic risk score for education (education PGS) and cognitive change. Using the most recent education PGS, we find that individuals with higher scores perform better across all measures of cognition in later life. Education PGS is associated with a faster decline in episodic memory in old age. The relationships are robust even after controlling for phenotypic educational attainment, and are unlikely to be driven by mortality bias. Future research should consider genetic effects when examining non-genetic factors in cognitive decline. Our findings represent a need to understand the mechanisms between genetic endowment of educational attainment and cognitive decline from a biological angle.

VL - 239 UR - https://www.ncbi.nlm.nih.gov/pubmed/31546143 U1 - http://www.ncbi.nlm.nih.gov/pubmed/31546143?dopt=Abstract ER - TY - JOUR T1 - Using Polygenic Scores in Social Science Research: Unraveling Childlessness JF - Frontiers in Sociology Y1 - 2019 A1 - Verweij, Renske M. A1 - Melinda C Mills A1 - Stulp, Gert A1 - Ilja M Nolte A1 - Nicola Barban A1 - Felix C Tropf A1 - Carrell, Douglas T. A1 - Aston, Kenneth I. A1 - Krina T Zondervan A1 - Rahmioglu, Nilufer A1 - Dalgaard, Marlene A1 - Skaarup, Carina A1 - Hayes, M. Geoffrey A1 - Dunaif, Andrea A1 - Guo, Guang A1 - Snieder, Harold KW - childlessness KW - polygenic score KW - social science AB - Biological, genetic, and socio-demographic factors are all important in explaining reproductive behavior, yet these factors are typically studied in isolation. In this study, we explore an innovative sociogenomic approach, which entails including key socio-demographic (marriage, education, occupation, religion, cohort) and genetic factors related to both behavioral [age at first birth (AFB), number of children ever born (NEB)] and biological fecundity-related outcomes (endometriosis, age at menopause and menarche, polycystic ovary syndrome, azoospermia, testicular dysgenesis syndrome) to explain childlessness. We examine the association of all sets of factors with childlessness as well as the interplay between them. We derive polygenic scores (PGS) from recent genome-wide association studies (GWAS) and apply these in the Health and Retirement Study (N = 10,686) and Wisconsin Longitudinal Study (N = 8,284). Both socio-demographic and genetic factors were associated with childlessness. Whilst socio-demographic factors explain 19–46% in childlessness, the current PGS explains <1% of the variance, and only PGSs from large GWASs are related to childlessness. Our findings also indicate that genetic and socio-demographic factors are not independent, with PGSs for AFB and NEB related to education and age at marriage. The explained variance by polygenic scores on childlessness is limited since it is largely a behavioral trait, with genetic explanations expected to increase somewhat in the future with better-powered GWASs. As genotyping of individuals in social science surveys becomes more prevalent, the method described in this study can be applied to other outcomes. VL - 4 UR - https://www.frontiersin.org/article/10.3389/fsoc.2019.00074 ER - TY - JOUR T1 - The Sociogenomics of Polygenic Scores of Reproductive Behavior and Their Relationship to Other Fertility Traits JF - RSF: The Russell Sage Foundation Journal of the Social Sciences Y1 - 2018 A1 - Melinda C Mills A1 - Nicola Barban A1 - Felix C Tropf KW - Education KW - Fertility KW - Genetics KW - GWAS KW - PGS AB - Human reproductive behavior until relatively recently has been explained exclusively via individual and social characteristics. This article applies results from a recent Genome-Wide Association Study that combined sixty-two data sources to isolate twelve genetic loci associated with reproductive behavior. We create polygenic scores that allow us to include a summary variable of genetic factors into our statistical models. We use four datasets: the U.S. Health and Retirement Study, Dutch LifeLines, TwinsUK and the Swedish Twin register. First, we provide a brief overview of the dominant explanations of reproductive behavior. Second, we test the predictive power of polygenic scores. Third, we interrogate the robustness of our models using a series of sensitivity analyses to take into account possible confounders due to population stratification and selection. VL - 4 UR - http://www.jstor.org/stable/10.7758/rsf.2018.4.4.07 IS - 4 JO - RSF: The Russell Sage Foundation Journal of the Social Sciences ER - TY - JOUR T1 - Genome-wide analysis identifies 12 loci influencing human reproductive behavior. JF - Nat Genet Y1 - 2016 A1 - Nicola Barban A1 - Jansen, Rick A1 - de Vlaming, Ronald A1 - Vaez, Ahmad A1 - Mandemakers, Jornt J A1 - Felix C Tropf A1 - Shen, Xia A1 - James F Wilson A1 - Daniel I Chasman A1 - Ilja M Nolte A1 - Tragante, Vinicius A1 - van der Laan, Sander W A1 - Perry, John R B A1 - Kong, Augustine A1 - Ahluwalia, Tarunveer S A1 - Albrecht, Eva A1 - Laura M Yerges-Armstrong A1 - Atzmon, Gil A1 - Auro, Kirsi A1 - Kristin L. Ayers A1 - Bakshi, Andrew A1 - Ben-Avraham, Danny A1 - Klaus Berger A1 - Bergman, Aviv A1 - Bertram, Lars A1 - Bielak, Lawrence F A1 - Bjornsdottir, Gyda A1 - Bonder, Marc Jan A1 - Broer, Linda A1 - Bui, Minh A1 - Barbieri, Caterina A1 - Cavadino, Alana A1 - Chavarro, Jorge E A1 - Turman, Constance A1 - Maria Pina Concas A1 - Cordell, Heather J A1 - Gail Davies A1 - Eibich, Peter A1 - Eriksson, Nicholas A1 - Tõnu Esko A1 - Eriksson, Joel A1 - Falahi, Fahimeh A1 - Felix, Janine F A1 - Mark Alan Fontana A1 - Lude L Franke A1 - Gandin, Ilaria A1 - Gaskins, Audrey J A1 - Gieger, Christian A1 - Gunderson, Erica P A1 - Guo, Xiuqing A1 - Caroline Hayward A1 - He, Chunyan A1 - Edith Hofer A1 - Huang, Hongyan A1 - Joshi, Peter K A1 - Kanoni, Stavroula A1 - Karlsson, Robert A1 - Kiechl, Stefan A1 - Kifley, Annette A1 - Kluttig, Alexander A1 - Kraft, Peter A1 - Lagou, Vasiliki A1 - Lecoeur, Cecile A1 - Lahti, Jari A1 - Li-Gao, Ruifang A1 - Penelope A Lind A1 - Tian Liu A1 - Makalic, Enes A1 - Mamasoula, Crysovalanto A1 - Lindsay K Matteson A1 - Mbarek, Hamdi A1 - McArdle, Patrick F A1 - McMahon, George A1 - Meddens, S Fleur W A1 - Mihailov, Evelin A1 - Michael B Miller A1 - Missmer, Stacey A A1 - Monnereau, Claire A1 - van der Most, Peter J A1 - Myhre, Ronny A1 - Michael A Nalls A1 - Nutile, Teresa A1 - Ioanna Panagiota Kalafati A1 - Porcu, Eleonora A1 - Prokopenko, Inga A1 - Rajan, Kumar B A1 - Rich-Edwards, Janet A1 - Cornelius A Rietveld A1 - Robino, Antonietta A1 - Rose, Lynda M A1 - Rueedi, Rico A1 - Ryan, Kathleen A A1 - Saba, Yasaman A1 - Schmidt, Daniel A1 - Jennifer A Smith A1 - Stolk, Lisette A1 - Streeten, Elizabeth A1 - Tönjes, Anke A1 - Thorleifsson, Gudmar A1 - Ulivi, Sheila A1 - Wedenoja, Juho A1 - Jürgen Wellmann A1 - Willeit, Peter A1 - Yao, Jie A1 - Yengo, Loic A1 - Jing Hua Zhao A1 - Wei Zhao A1 - Zhernakova, Daria V A1 - Amin, Najaf A1 - Andrews, Howard A1 - Balkau, Beverley A1 - Barzilai, Nir A1 - Bergmann, Sven A1 - Biino, Ginevra A1 - Bisgaard, Hans A1 - Bønnelykke, Klaus A1 - Dorret I Boomsma A1 - Buring, Julie E A1 - Campbell, Harry A1 - Cappellani, Stefania A1 - Ciullo, Marina A1 - Cox, Simon R A1 - Francesco Cucca A1 - Toniolo, Daniela A1 - Davey-Smith, George A1 - Ian J Deary A1 - George Dedoussis A1 - Deloukas, Panos A1 - Cornelia M van Duijn A1 - Eco J. C. de Geus A1 - Johan G Eriksson A1 - Jessica Faul A1 - Cinzia Felicita Sala A1 - Froguel, Philippe A1 - Paolo P. Gasparini A1 - Giorgia G Girotto A1 - Hans-Jörgen Grabe A1 - Greiser, Karin Halina A1 - Groenen, Patrick J F A1 - de Haan, Hugoline G A1 - Haerting, Johannes A1 - Tamara B Harris A1 - Andrew C Heath A1 - Heikkilä, Kauko A1 - Hofman, Albert A1 - Homuth, Georg A1 - Holliday, Elizabeth G A1 - John L Hopper A1 - Hyppönen, Elina A1 - Jacobsson, Bo A1 - Vincent Jaddoe A1 - Johannesson, Magnus A1 - Jugessur, Astanand A1 - Kähönen, Mika A1 - Kajantie, Eero A1 - Sharon L R Kardia A1 - Keavney, Bernard A1 - Kolcic, Ivana A1 - Koponen, Päivikki A1 - Kovacs, Peter A1 - Kronenberg, Florian A1 - Kutalik, Zoltán A1 - La Bianca, Martina A1 - Lachance, Genevieve A1 - Iacono, William G A1 - Lai, Sandra A1 - Lehtimäki, Terho A1 - David C Liewald A1 - Lindgren, Cecilia M A1 - Yongmei Liu A1 - Luben, Robert A1 - Lucht, Michael A1 - Luoto, Riitta A1 - Magnus, Per A1 - Patrik K E Magnusson A1 - Nicholas G Martin A1 - McGue, Matt A1 - McQuillan, Ruth A1 - Sarah E Medland A1 - Meisinger, Christa A1 - Mellström, Dan A1 - Andres Metspalu A1 - Traglia, Michela A1 - Lili Milani A1 - Mitchell, Paul A1 - Grant W Montgomery A1 - Dennis O Mook-Kanamori A1 - de Mutsert, Renée A1 - Nohr, Ellen A A1 - Ohlsson, Claes A1 - Olsen, Jørn A1 - Ong, Ken K A1 - Paternoster, Lavinia A1 - Pattie, Alison A1 - Brenda W J H Penninx A1 - Markus Perola A1 - Peyser, Patricia A A1 - Pirastu, Mario A1 - Polasek, Ozren A1 - Power, Chris A1 - Kaprio, Jaakko A1 - Raffel, Leslie J A1 - Katri Räikkönen A1 - Olli T Raitakari A1 - Ridker, Paul M A1 - Ring, Susan M A1 - Roll, Kathryn A1 - Rudan, Igor A1 - Ruggiero, Daniela A1 - Rujescu, Dan A1 - Veikko Salomaa A1 - Schlessinger, David A1 - Schmidt, Helena A1 - Schmidt, Reinhold A1 - Schupf, Nicole A1 - Johannes H Smit A1 - Sorice, Rossella A1 - Timothy Spector A1 - John M Starr A1 - Stöckl, Doris A1 - Strauch, Konstantin A1 - Stumvoll, Michael A1 - Swertz, Morris A A1 - Thorsteinsdottir, Unnur A1 - A. Roy Thurik A1 - Nicholas J Timpson A1 - Tung, Joyce Y A1 - André G Uitterlinden A1 - Vaccargiu, Simona A1 - Viikari, Jorma A1 - Vitart, Veronique A1 - Völzke, Henry A1 - Vollenweider, Peter A1 - Vuckovic, Dragana A1 - Waage, Johannes A1 - Wagner, Gert G A1 - Wang, Jie Jin A1 - Wareham, Nicholas J A1 - David R Weir A1 - Gonneke Willemsen A1 - Willeit, Johann A1 - Alan F Wright A1 - Krina T Zondervan A1 - Stefansson, Kari A1 - Krueger, Robert F A1 - Lee, James J A1 - Daniel J. Benjamin A1 - Cesarini, David A1 - Philipp D Koellinger A1 - den Hoed, Marcel A1 - Snieder, Harold A1 - Melinda C Mills AB -

The genetic architecture of human reproductive behavior-age at first birth (AFB) and number of children ever born (NEB)-has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the underlying mechanisms of AFB and NEB are poorly understood. We report a large genome-wide association study of both sexes including 251,151 individuals for AFB and 343,072 individuals for NEB. We identified 12 independent loci that are significantly associated with AFB and/or NEB in a SNP-based genome-wide association study and 4 additional loci associated in a gene-based effort. These loci harbor genes that are likely to have a role, either directly or by affecting non-local gene expression, in human reproduction and infertility, thereby increasing understanding of these complex traits.

VL - 48 IS - 12 U1 - http://www.ncbi.nlm.nih.gov/pubmed/27798627?dopt=Abstract ER -