Pitfalls in performing genome-wide association studies on ratio traits.

ABSTRACT: Genome-wide association studies (GWASs) are often performed on ratios composed of a numerator trait divided by a denominator trait. Examples include body mass index (BMI) and the waist-to-hip ratio, among many others. Explicitly or implicitly, the goal of forming the ratio is typically to adjust for an association between the numerator and denominator. While forming ratios may be clinically expedient, there are several important issues with performing GWAS on ratios. Forming a ratio does not "adjust" for the denominator in the sense of conditioning on it, and it is unclear whether associations with ratios are attributable to the numerator, the denominator, or both. Here we demonstrate that associations arising in ratio GWAS can be entirely denominator driven, implying that at least some as

SUBMITTER: McCaw ZR 

PROVIDER: S-EPMC11808723 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature