Genetic nature or genetic nurture? Introducing social genetic parameters to quantify bias in polygenic score analyses
Abstract
Results from a genome-wide association study (GWAS) can be used to generate a polygenic score (PGS), an individual-level measure summarizing identified genetic influence on a trait dispersed across the genome. For complex, behavioral traits, the association between an individual's PGS and their phenotype may contain bias (from geographic, ancestral, and/or socioeconomic confounding) alongside the causal effect of the individual's genes. We formalize the introduction of a different source of bias in regression models using PGSs: the effects of parental genes on offspring outcomes, known as genetic nurture. GWAS do not discriminate between the various pathways through which genes become associated with outcomes, meaning existing PGSs capture both direct genetic effects and genetic nurture effects. We construct a theoretical model for genetic effects and show that the presence of genetic nurture biases PGS coefficients from both naïve OLS (between-family) and family fixed effects (within-family) regressions. This bias is in opposite directions; while naïve OLS estimates are biased away from zero, family fixed effects estimates are biased toward zero. We quantify this bias using two novel parameters: (1) the genetic correlation between the direct and nurture effects and (2) the ratio of the SNP heritabilities for the direct and nurture effects.
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The within-family effect of cogPGS was roughly two-thirds of the between-family effect for intelligence at baseline, in line with the literature.
“We found the within-family effect of cogPGS to be roughly two-thirds of the between-family effect for intelligence (at baseline), in line with the literature43,44.”
From The impact of digital media on children’s intelligence while controlling for genetic differences in cognition and socioeconomic background (2022) · cites this paper as [44]
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Mental Health Effects of Income over the Adult Life Course
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Class, genes, and rationality: A gene–environment interaction approach to ideology
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Beyond Barker: Infant Mortality at Birth and Ischaemic Heart Disease in Older AgePreprint
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Exploring the Fetal Origins Hypothesis Using Genetic Data
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Self-citationConfounding fuels misinterpretation in human genetics
Benning, J. W., Carlson, J., Smith, O. S., Shaw, R. G., & Harpak, A. (2025) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.2025.1615 · Cited by 5 · see citing works
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Decomposing heritability and genetic covariance by direct and indirect effect paths
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A Wolf in Sheep's Clothing: Idealisations and the aims of polygenic scores
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Exploring Genetic Influences on Birth WeightPreprint
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Self-citationDoes standard adjustment for genomic population structure capture direct genetic effects?Preprint
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Genetics for ‘equality’? The politics of knowledge production in educational genomics
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Quantifying direct genetic signal captured by principal component adjustment
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Self-citationGenetic Endowments, Income Dynamics, and Wealth Accumulation Over the LifecyclePreprint
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Economic Preferences, Genes, and Childhood DisadvantagePreprint
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Genetic risk for ADHD and later-life health and wellbeing: individual and spousal spillovers
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Ethical Priorities Among Commercial Genomics Professionals
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- Authors
- Trejo, S., & Domingue, B. W.
- Affiliations
- Stanford University (US)
- Corresponding author
- Trejo, Sam
- Venue
- Biodemography and Social Biology
- Publisher
- Informa UK Limited
- Published
- 2018-10-02
- Volume
- 64
- Issue
- 3-4
- Pages
- 187-215
- ISSN
- 1948-5565 (ISSN-L)
- 1948-5573
- OpenAlex
- W2996316818
- Cited by
- 69
- References
- 57
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 14 · 2023: 7 · 2022: 11 · 2021: 13 · 2020: 6
- FWCI
- 2.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biodemography and Social Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and phenotypic traits in livestock
- Social Sciences › Sociology and Political Science › Intergenerational and Educational Inequality Studies
- Keywords
- polygenic risk score, genetic nurture, direct genetic effects, family fixed effects, genetic correlation, SNP heritability
- MeSH terms
- Genotype, Humans, Models, Genetic, Phenotype, Bias, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Genome-Wide Association Study
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