“Polygenic Risk Scores Applied to a Single Cohort Reveal Pleiotropy among Hundreds of Human Phenotypes”, 2017-10-14 (; backlinks; similar):
Background: There is now convincing evidence that pleiotropy across the genome contributes to the correlation between human traits and comorbidity of diseases. The recent availability of genome-wide association study (GWAS) results have made the polygenic risk score (PRS) approach a powerful way to perform genetic prediction and identify genetic overlap among phenotypes.
Methods & Findings
Here we use the PRS method to assess evidence for shared genetic aetiology across hundreds of traits within a single epidemiological study—the Northern Finland Birth Cohort 1966 (NFBC196658ya). We replicate numerous recent findings, such as a genetic association between Alzheimer’s disease and lipid levels, while the depth of phenotyping in the NFBC1966 highlights a range of novel genetic associations between traits.
Conclusion: This study illustrates the power in taking a hypothesis-free approach to the study of shared genetic aetiology between human traits and diseases. It also demonstrates the potential of the PRS method to provide important biological insights using only a single well-phenotyped epidemiological study of moderate sample size (~5k), with important advantages over evaluating genetic correlations from GWAS summary statistics only.