Causal effects on complex traits are similar for common variants across segments of different continental ancestries within admixed individuals

Kangcheng Hou, Yi Ding, Ziqi Xu, Yue Wu, Arjun Bhattacharya, Rachel Mester, Gillian M. Belbin, Steve Buyske, David V. Conti, Burcu F. Darst, Myriam Fornage, Chris Gignoux, Xiuqing Guo, Christopher Haiman, Eimear E. Kenny, Michelle Kim, Charles Kooperberg, Leslie Lange, Ani Manichaikul, Kari E. NorthUlrike Peters, Laura J. Rasmussen-Torvik, Stephen S. Rich, Jerome I. Rotter, Heather E. Wheeler, Genevieve L. Wojcik, Ying Zhou, Sriram Sankararaman, Bogdan Pasaniuc

Research output: Contribution to journalArticlepeer-review

Abstract

Individuals of admixed ancestries (for example, African Americans) inherit a mosaic of ancestry segments (local ancestry) originating from multiple continental ancestral populations. This offers the unique opportunity of investigating the similarity of genetic effects on traits across ancestries within the same population. Here we introduce an approach to estimate correlation of causal genetic effects (radmix) across local ancestries and analyze 38 complex traits in African-European admixed individuals (N = 53,001) to observe very high correlations (meta-analysis radmix = 0.95, 95% credible interval 0.93–0.97), much higher than correlation of causal effects across continental ancestries. We replicate our results using regression-based methods from marginal genome-wide association study summary statistics. We also report realistic scenarios where regression-based methods yield inflated heterogeneity-by-ancestry due to ancestry-specific tagging of causal effects, and/or polygenicity. Our results motivate genetic analyses that assume minimal heterogeneity in causal effects by ancestry, with implications for the inclusion of ancestry-diverse individuals in studies.

Original languageEnglish (US)
Pages (from-to)549-558
Number of pages10
JournalNature genetics
Volume55
Issue number4
DOIs
StatePublished - Apr 2023

ASJC Scopus subject areas

  • Genetics

Fingerprint

Dive into the research topics of 'Causal effects on complex traits are similar for common variants across segments of different continental ancestries within admixed individuals'. Together they form a unique fingerprint.

Cite this