ArticleNature genetics2025
Family-based genome-wide association study designs for increased power and robustness.
Article in Nature genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 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
- [Association analysis between genetic nurturing effects ofBeijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2026Article
- Neurobehavioural genes exert indirect genetic effects on blood lipid profiles through behavioural traits.Communications biology · 2026Article
- Estimation of direct and indirect polygenic effects and gene-environment interactions using polygenic scores in case-parent trio studies.Nature genetics · 2026Article
- Genomic-Relatedness Matching Expands Population Coverage, Improves Power, and Reduces Bias in Genetic Association Analyses.medRxiv : the preprint server for health sciences · 2026Article
- On the genetic origins of phenotypes in genome-wide association studies: the SAFE-hBMC bioinformatics · 2026Article
- Dissecting the Predictive Accuracy of Polygenic Indexes for Behavioral Phenotypes Across Genetic Ancestries.bioRxiv : the preprint server for biology · 2026Article
- Genetic Burden andJournal of personalized medicine · 2026Article
- Methods for modeling gene-environment interplay using polygenic risk scores.Statistical applications in genetics and molecular biology · 2026Review
- Improving estimation efficiencies for family-based GWAS by integrating large external data.medRxiv : the preprint server for health sciences · 2025Article
- Dissecting the Predictive Accuracy of Polygenic Indexes for Behavioral Phenotypes Across Genetic Ancestries.Research square · 2025Article
- Efficient Mendelian randomization analysis with self-adaptive determination of sample structure and multiple pleiotropic effects.American journal of human genetics · 2025Article
- Estimation of Direct and Indirect Polygenic Effects and Gene-Environment Interactions using Polygenic Scores in Case-Parent Trio Studies.medRxiv : the preprint server for health sciences · 2025Article
- Cohort profile: Copenhagen Hospital Biobank-chronic inflammatory disease-inflammatory bowel disease (CHB-CID:IBD) genetic cohort.European journal of epidemiology · 2025Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Family-based genome-wide association studies (FGWASs) use random, within-family genetic variation to remove confounding from estimates of direct genetic effects (DGEs). Here we introduce a 'unified estimator' that includes individuals without genotyped relatives, unifying standard and FGWAS while increasing power for DGE estimation. We also introduce a 'robust estimator' that is not biased in structured and/or admixed populations. In an analysis of 19 phenotypes in the UK Biobank, the unified estimator in the White British subsample and the robust estimator (applied without ancestry restrictions) increased the effective sample size for DGEs by 46.9% to 106.5% and 10.3% to 21.0%, respectively, compared to using genetic differences between siblings. Polygenic predictors derived from the unified estimator demonstrated superior out-of-sample prediction ability compared to other family-based methods. We implemented the methods in the software package snipar in an efficient linear mixed model that accounts for sample relatedness and sibling shared environment.
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