Shared associations identify causal relationships between gene expression and immune cell phenotypes

Commun Biol. 2021 Mar 4;4(1):279. doi: 10.1038/s42003-021-01823-w.

Abstract

Genetic mapping studies have identified thousands of associations between common variants and hundreds of human traits. Translating these associations into mechanisms is complicated by two factors: they fall into gene regulatory regions; and they are rarely mapped to one causal variant. One way around these limitations is to find groups of traits that share associations, using this genetic link to infer a biological connection. Here, we assess how many trait associations in the same locus are due to the same genetic variant, and thus shared; and if these shared associations are due to causal relationships between traits. We find that only a subset of traits share associations, with many due to causal relationships rather than pleiotropy. We therefore suggest that simply observing overlapping associations at a genetic locus is insufficient to infer causality; direct evidence of shared associations is required to support mechanistic hypotheses in genetic studies of complex traits.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Gene Expression Regulation
  • Genetic Association Studies
  • Genetic Variation*
  • Genotype
  • Healthy Volunteers
  • Humans
  • Immune System / cytology*
  • Immunophenotyping
  • Mendelian Randomization Analysis
  • Phenotype
  • Quantitative Trait Loci*
  • Transcriptome