Does genetic predisposition modify the effect of lifestyle-related factors on DNA methylation?

C Yu; AM Hodge; EM Wong; JE Joo; E Makalic; DF Schmidt; DD Buchanan; G Severi; JL Hopper; DR English; GG Giles; RL Milne; MC Southey; PA Dugué

Journal article

Does genetic predisposition modify the effect of lifestyle-related factors on DNA methylation?

C Yu, AM Hodge, EM Wong, JE Joo, E Makalic, DF Schmidt, DD Buchanan, G Severi, JL Hopper, DR English, GG Giles, RL Milne, MC Southey, PA Dugué

Epigenetics | TAYLOR & FRANCIS INC | Published : 2022

DOI: 10.1080/15592294.2022.2088038

Abstract

Lifestyle-related phenotypes have been shown to be heritable and associated with DNA methylation. We aimed to investigate whether genetic predisposition to tobacco smoking, alcohol consumption, and higher body mass index (BMI) moderates the effect of these phenotypes on blood DNA methylation. We calculated polygenic scores (PGS) to quantify genetic predisposition to these phenotypes using training (N = 7,431) and validation (N = 4,307) samples. Using paired genetic-methylation data (N = 4,307), gene–environment interactions (i.e., PGS × lifestyle) were assessed using linear mixed-effects models with outcomes: 1) methylation at sites found to be strongly associated with smoking (1,061 CpGs), ..

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University of Melbourne Researchers

Allison Hodge Author

Eric Joo Author

Enes Makalic Author

Daniel Schmidt Author Melbourne School of Population and Global Health

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Grants

Awarded by VicHealth

Funding Acknowledgements

MCCS cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian NHMRC grants 209057, 251553, and 504711 and by infrastructure provided by Cancer Council Victoria. The nested case-control methylation studies were supported by the NHMRC grants 1011618, 1026892, 1027505, 1050198, 1043616, and 1074383. This work was further supported by NHMRC grant 1164455. M.C.S. is a recipient of a Senior Research Fellowship from the NHMRC (GTN1155163).