Widespread covariation of early environmental exposures and trait-associated polygenic variation

Krapohl, E. et al. (2017) Widespread covariation of early environmental exposures and trait-associated polygenic variation. Proceedings of the National Academy of Sciences of the United States of America, 114(44), pp. 11727-11732. (doi: 10.1073/pnas.1707178114) (PMID:29078306) (PMCID:PMC5676894)

Abstract

Although gene–environment correlation is recognized and investigated by family studies and recently by SNP-heritability studies, the possibility that genetic effects on traits capture environmental risk factors or protective factors has been neglected by polygenic prediction models. We investigated covariation between trait-associated polygenic variation identified by genome-wide association studies (GWASs) and specific environmental exposures, controlling for overall genetic relatedness using a genomic relatedness matrix restricted maximum-likelihood model. In a UK-representative sample (n = 6,710), we find widespread covariation between offspring trait-associated polygenic variation and parental behavior and characteristics relevant to children’s developmental outcomes—independently of population stratification. For instance, offspring genetic risk for schizophrenia was associated with paternal age (R2 = 0.002; P = 1e-04), and offspring education-associated variation was associated with variance in breastfeeding (R2 = 0.021; P = 7e-30), maternal smoking during pregnancy (R2 = 0.008; P = 5e-13), parental smacking (R2 = 0.01; P = 4e-15), household income (R2 = 0.032; P = 1e-22), watching television (R2 = 0.034; P = 5e-47), and maternal education (R2 = 0.065; P = 3e-96). Education-associated polygenic variation also captured covariation between environmental exposures and children’s inattention/hyperactivity, conduct problems, and educational achievement. The finding that genetic variation identified by trait GWASs partially captures environmental risk factors or protective factors has direct implications for risk prediction models and the interpretation of GWAS findings.

• Item Type: Articles
• Additional Information: TEDS is supported by UK Medical Research Council Program Grant MR/M021475/1 (and previously Grant G0901245) (to R.P.), with additional support from National Institutes of Health Grant AG046938. The research leading to these results has also received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013)/Grant Agreement 602768 and ERC Grant Agreement 295366. R.P. is supported by Medical Research Council Professorship Award G19/2. E.K. is supported by the MRC/IoPPN Excellence Award. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This study presents independent research supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the authors and not necessarily those of the NHS, NIHR, Department of Health or King’s College London. We gratefully acknowledge capital equipment funding from Maudsley Charity Grant Ref. 980 and Guy’s and St Thomas’s Charity Grant Ref. STR130505. S.J.N. is also supported by the NIHR University College London Hospitals Biomedical Research Centre, and by awards establishing the Farr Institute of Health Informatics Research at UCLPartners, from the Medical Research Council, Arthritis Research UK, British Heart Foundation, Cancer Research UK, Chief Scientist Office, Economic and Social Research Council, Engineering and Physical Sciences Research Council, NIHR, National Institute for Social Care and Health Research, and Wellcome Trust (Grant MR/ K006584/1). P.F.O. receives funding from the UK Medical Research Council (Grant MR/N015746/1) and the Wellcome Trust (Grant 109863/Z/15/Z). L.J.H. is supported by an Economic and Social Research Council multidisciplinary studentship.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Hannigan, Dr Laurie
• Authors: Krapohl, E., Hannigan, L.J., Pingault, J.-B., Patel, H., Kadeva, N., Curtis, C., Breen, G., Newhouse, S.J., Eley, T.C., O’Reilly, P.F., and Plomin, R.
• College/School: College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Public Health
• Journal Name: Proceedings of the National Academy of Sciences of the United States of America
• Publisher: National Academy of Sciences
• ISSN: 0027-8424
• ISSN (Online): 1091-6490
• Published Online: 16 October 2017