Causal effects on complex traits are similar for common variants across segments of different continental ancestries within admixed individuals.
Nat Genet
; 55(4): 549-558, 2023 04.
Article
in En
| MEDLINE
| ID: mdl-36941441
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Multifactorial Inheritance
/
Genetics, Population
Type of study:
Systematic_reviews
Limits:
Humans
Language:
En
Journal:
Nat Genet
Journal subject:
GENETICA MEDICA
Year:
2023
Document type:
Article
Affiliation country:
Estados Unidos