Extending the Use of Mendelian Randomisation With Non‐Inherited Variants to Assess Socially Transmitted Parental Exposures Under Assortative Mating
Year: 2026
Type: article
Abstract: A longstanding aim of developmental psychology and epidemiology is to understand the causal effects of parental phenotypes on offspring outcomes. Traditional approaches often fail to account for confounding and reverse causation. We evaluate the use of Mendelian randomisation with non-inherited variants (MR-NIV) to address these limitations. MR-NIV leverages non-inherited genetic variants to instrument the parental phenotype independent of the offspring's genotype. We used Directed Acyclic Graphs and simulations to validate MR-NIV and explore robustness to assortative mating. In contrast to an alternative MR method which adjusts the parental genotype for offspring genotype, MR-NIV can be robust to assortative mating when used without trio data. In settings without trio data, MR-NIV outperformed the adjustment method. The adjustment method outperformed MR-NIV in settings with trio data. Applying MR-NIV to the Avon Longitudinal Study of Parents and Children, we assessed the causal effect of parental smoking on offspring smoking initiation at age 16. Results were consistent with observational studies, suggesting a meaningful increase in the risk of offspring smoking due to parental smoking. However, larger sample sizes will be necessary to provide a precise answer. MR-NIV offers a promising extension of Mendelian randomisation for studying the developmental environment.
Source: Genetic Epidemiology
DOI: 10.1002/gepi.70031
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,150
Awards: G1211085472, G1492920458, G1605161196, New horizons in Mendelian randomization, G2165920734, Large-scale integrative genomic studies of high-dimensional traits in cardiovascular diseases (renewal), G2537968379, G2797452859, G2813796156, Research Excellence (round 3), G3507283293, The Avon Longitudinal Study of Parents and Children (ALSPAC): A multi- generation, longitudinal resource focusing on life course health and well- being., G4124815159, G4140337337, Statistical Methods for Causal Inference, The Avon Longitudinal Study for Parents and Children: An international resource for population genomic and lifecourse epidemiology. Core programme support 2014-2019., G4962914553, New horizons in Mendelian randomization, Large-scale integrative molecular studies of CVDs in multi-ethnic cohorts, G5307399816, G5857625837, South West Doctoral Training Partnership (SWDTP), G6476865236, G6787924332, G705064920, G7095874527, The BHF Chair of Epidemiology and Medicine, G792825315, The Avon Longitudinal Study of Parents and Children (ALSPAC): A multi-generation, longitudinal resource focusing on life course health and well-being., G7988709377, G8182453687, G824700880, G8347284120, Behavioural, Social and Environmental Determinants of Physical and Mental Health
OpenAlex ID: W7125112042