Proxy gene-by-environment Mendelian randomization study confirms a causal effect of maternal smoking on offspring birthweight, but little evidence of long-term influences on offspring health.

ABSTRACT:

Background

A lack of genetic data across generations makes transgenerational Mendelian randomization (MR) difficult. We used UK Biobank and a novel proxy gene-by-environment MR to investigate effects of maternal smoking heaviness in pregnancy on offspring health, using participants' (generation one: G1) genotype (rs16969968 in CHRNA5) as a proxy for their mothers' (G0) genotype.

Methods

We validated this approach by replicating an established effect of maternal smoking heaviness on offspring birthweight. Then we applied this approach to explore effects of maternal (G0) smoking heaviness on offspring (G1) later life outcomes and on birthweight of G1 women's children (G2).

Results

Each additional smoking-increasing allele in offspring (G1) was associated with a 0.018 [9

SUBMITTER: Yang Q 

PROVIDER: S-EPMC7660158 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature