ArticlePloS one2024
Interpreting polygenic score effects in sibling analysis.
Article in PloS one, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Within-sibling attenuation of polygenic risk score accuracy: investigating the effects of principal component analysis, LD score regression, and mixed model association in the UK Biobank.Human genetics · 2026Article
- Quantifying direct genetic signal captured by principal component adjustment.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Genetics and Socioeconomic Status: Some Preliminary Evidence on Mechanisms.Journal of political economy microeconomics · 2025Article
- Using twin-pairs to assess potential bias in polygenic prediction of externalising behaviours across development.Molecular psychiatry · 2025Article
- The contribution of attention-deficit/hyperactivity disorder polygenic load to metabolic and cardiovascular health outcomes: a large-scale population and sibling study.Translational psychiatry · 2024Article
- Genetic associations between non-cognitive skills and academic achievement over development.Nature human behaviour · 2024Article
- Causal interpretations of family GWAS in the presence of heterogeneous effects.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Polygenic Indices (a.k.a. Polygenic Scores) in Social Science: A Guide for Interpretation and Evaluation.Sociological methodology · 2024Article
- Interpreting population- and family-based genome-wide association studies in the presence of confounding.PLoS biology · 2024Article
- More than nature and nurture, indirect genetic effects on children's academic achievement are consequences of dynastic social processes.Nature human behaviour · 2024Article
- The structure of psychiatric comorbidity without selection and assortative mating.Translational psychiatry · 2024Article
- Correlates of Risk for Disinhibited Behaviors in the Million Veteran Program Cohort.JAMA psychiatry · 2024Article
- Causal interpretations of family GWAS in the presence of heterogeneous effects.bioRxiv : the preprint server for biology · 2023Article
- Genetic contributions of noncognitive skills to academic development.bioRxiv : the preprint server for biology · 2023Article
- Educational attainment, health outcomes and mortality: a within-sibship Mendelian randomization study.International journal of epidemiology · 2023Article
- Genetic contributions of noncognitive skills to academic development.Research square · 2023Article
- Interpreting population and family-based genome-wide association studies in the presence of confounding.bioRxiv : the preprint server for biology · 2023Article
- Luck, lottery, or legacy? The problem of confounding. A reply to Harden.Evolution; international journal of organic evolution · 2022Article
- Using a polygenic score in a family design to understand genetic influences on musicality.Scientific reports · 2022Article
- Estimating effects of parents' cognitive and non-cognitive skills on offspring education using polygenic scores.Nature communications · 2022Article
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Authors and funding
4 authors.
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Abstract
Researchers often claim that sibling analysis can be used to separate causal genetic effects from the assortment of biases that contaminate most downstream genetic studies (e.g. polygenic score predictors). Indeed, typical results from sibling analysis show large (>50%) attenuations in the associations between polygenic scores and phenotypes compared to non-sibling analysis, consistent with researchers' expectations about bias reduction. This paper explores these expectations by using family (quad) data and simulations that include indirect genetic effect processes and evaluates the ability of sibling analysis to uncover direct genetic effects of polygenic scores. We find that sibling analysis, in general, fail to uncover direct genetic effects; indeed, these models have both upward and downward biases that are difficult to sign in typical data. When genetic nurture effects exist, sibling analysis creates "measurement error" that attenuates associations between polygenic scores and phenotypes. As the correlation between direct and indirect effect changes, this bias can increase or decrease. Our findings suggest that interpreting results from sibling analysis aimed at uncovering direct genetic effects should be treated with caution.
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