Hiring in life sciences? Share your open positions with our professional community. Read more Close

Advertisement

Multi-ancestry gene expression models amplify transcriptome-wide association study discovery and validation.

Created on 05 Jul 2026

Authors

Xavier Bledsoe, Nathan Watkins, Tavian Bowen-Moore, Marlisa Shaw, Ravi V Shah, Eric R Gamazon

Published in

Nature communications. Jul 04, 2026. Epub Jul 04, 2026.

Abstract

Our understanding of the influence of ancestral background on genetically determined expression remains limited, especially when gene expression models are applied to studies from different or multiple populations. We perform transcriptome-wide association studies of 6 psychiatric conditions, leveraging gene expression models trained in cohorts with different proportions of African, European, and Indigenous American genetic ancestries. For comparison, we repeat each transcriptome-wide association study using a model trained in individuals of predominantly European ancestry. We identify 1416 statistically significant gene-level associations (false discovery rate adjusted p < 0.05) across the 6 diagnoses, of which 62% are uniquely detected by the admixed gene models. Notably, we observe high correlation (ρ>0.92) in the gene-level effects on disease risk across ancestries, a statistic that remains robust for results that only reach statistical significance in one population. The genes identified by the admixed models implicate more neurophysiological features (as measured by brain imaging) associated with diagnostic symptoms. Overall, admixed gene expression models greatly extend the yield of transcriptome-wide association studies and substantially enhance validation, enabling more precise mapping of genetic effects to underlying pathophysiological mechanisms and highlighting potential avenues for therapeutic development.

PMID:
42401576
Bibliographic data and abstract were imported from PubMed on 05 Jul 2026.

Read full publication at:
Please sign in to see all details.

Advertisement

Stats

  • Community rating n/a 0 votes
  • Reviewers' rating n/a 0 votes
  • Your rating

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

  • Recommendations n/a n/a positive of 0 vote(s)
  • Views 3
  • Comments 0

Recommended by

  • No recommendations yet.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.

Advertisement