Genetic factor analysis for characterizing phenome-wide patterns of genetic pleiotropy.

Genetic factor analysis (GFA) identifies 15 pleiotropic components in heritability of 22 risk factors for coronary artery disease and type 2 diabetes.

• Why it matters: Understanding shared genetic influences across traits helps reveal biological mechanisms underlying complex diseases, but existing methods struggle with sample overlap and trait correlation.
• What they did: GFA automatically determines the number of factors, accounts for sample overlap, and allows non-orthogonal factors, applied to 22 risk factors and blood cell phenotypes, including multivariable Mendelian randomization.
• The result: Accounting for sample overlap was essential for biologically meaningful interpretations, enabling more precise insights into shared genetic architecture and biological processes.