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Significance It has been shown that human genomes can affect phenotype both directly (through inherited genetic variants) and indirectly (through parents and the family environment they create). Due to the correlation between parental and offspring genotypes, a standard genome-wide association study (GWAS) captures both the direct and indirect genetic effects. In this study, we introduce a statistical framework named DONUTS to estimate direct and indirect effects using summary statistics from GWAS conducted on own and offspring phenotypes. It requires only GWAS summary statistics as input, allows differential paternal and maternal effects, and accounts for sample overlap and assortative mating. DONUTS provides deeper etiological insights for complex traits and has practical guidance on future study designs.

Estimating genetic nurture with summary statistics of multigenerational genome-wide association studies