Within-family effect of ancestry on complex traits in a Mexican population
8 affiliations
- 1Nuffield Department of Population Health, University of Oxford, Oxford, UK
- 2Experimental Research Unit from the Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico
- 3Centre for AgriBioscience, Agriculture Victoria, Melbourne, Victoria Australia
- 4Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Parkville, Victoria Australia
- 5Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland Australia
- 6Human Genetics Department, UCLA David Geffen School of Medicine, Los Angeles, CA USA
- 7Tecnológico de Monterrey, Proyecto OriGen, Monterrey, Mexico
- 8Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico
Abstract
Human populations differ in disease prevalence and phenotypes, but the extent to which differences are caused by genetic factors is unknown for most complex traits. Comparing phenotypic means across populations is confounded by environmental differences and using polygenic predictors can lead to biased inference1,2. Family-based analyses of people of genetically admixed ancestry enable estimation of ancestry effects unconfounded by ancestry–environment correlations. Here we leverage genetic data from admixed adults in the Mexico City Prospective Study3,4 to estimate within-family ancestry effects5. We assessed genetic ancestry and 15 complex traits in 52,583 unrelated people and 39,714 relatives from 17,627 families. At the population level, relative to European ancestry, the effect of Indigenous American ancestry was −1.98 s.d. (P < 2 × 10−16) for height and a natural log odds ratio of 1.73 (95% confidence interval, 1.54–1.92) for type 2 diabetes. Within families, the effect of Indigenous American ancestry was −1.51 s.d. (P = 10−8) for height and natural log odds ratio of 5.13 (95% confidence interval, 2.48–7.78) for type 2 diabetes. These effects are supported by between-ancestry differences in trait-increasing allele counts and evidence of selection at trait-associated loci. We found no within-family ancestry effect on educational attainment or other traits despite significant associations at the population level, implying environmental causes or confounding. Overall, this study provides an experimental design to study between-ancestry genetic effects and identifies significant ancestry differences for height, type 2 diabetes and metabolic traits in a genetically diverse population from Mexico City.
Related
- Decomposing population differences in type 2 diabetes through a high-resolution GWAS of ~600,000 individuals with East Asian ancestry
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- PHATE-Derived Ancestry Coordinates Capture Continuous Population Structure in Human Genomic Data
- An iPSC-based experimental framework for investigating phenotypic variation associated with Jomon ancestry in the present-day Japanese population
BibTeX
@article{wang2026withinfamily,
title = {{Within-family effect of ancestry on complex traits in a Mexican population}},
author = {Siqi Wang and Jaime Berumen and Alejandra Vergara-Lope and Paulina Baca and Elizabeth Barrera and Fernando Rivas and Diego Aguilar-Ramirez and Rory Collins and Jonathan R. Emberson and Michael Hill and Michael E. Goddard and Loic Yengo and Alexander Strudwick Young and Jesus Alegre-Díaz and Pablo Kuri-Morales and Roberto Tapia-Conyer and Jason M. Torres and Peter M. Visscher},
journal = {Nature},
year = {2026},
month = sep,
doi = {10.1038/s41586-026-11039-9},
url = {https://doi.org/10.1038/s41586-026-11039-9},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Within-family effect of ancestry on complex traits in a Mexican population
AU - Siqi Wang
AU - Jaime Berumen
AU - Alejandra Vergara-Lope
AU - Paulina Baca
AU - Elizabeth Barrera
AU - Fernando Rivas
AU - Diego Aguilar-Ramirez
AU - Rory Collins
AU - Jonathan R. Emberson
AU - Michael Hill
AU - Michael E. Goddard
AU - Loic Yengo
AU - Alexander Strudwick Young
AU - Jesus Alegre-Díaz
AU - Pablo Kuri-Morales
AU - Roberto Tapia-Conyer
AU - Jason M. Torres
AU - Peter M. Visscher
PY - 2026
DA - 2026/09/09
JO - Nature
DO - 10.1038/s41586-026-11039-9
UR - https://doi.org/10.1038/s41586-026-11039-9
AB - Human populations differ in disease prevalence and phenotypes, but the extent to which differences are caused by genetic factors is unknown for most complex traits. Comparing phenotypic means across populations is confounded by environmental differences and using polygenic predictors can lead to biased inference1,2. Family-based analyses of people of genetically admixed ancestry enable estimation of ancestry effects unconfounded by ancestry–environment correlations. Here we leverage genetic data from admixed adults in the Mexico City Prospective Study3,4 to estimate within-family ancestry effects5. We assessed genetic ancestry and 15 complex traits in 52,583 unrelated people and 39,714 relatives from 17,627 families. At the population level, relative to European ancestry, the effect of Indigenous American ancestry was −1.98 s.d. (P < 2 × 10−16) for height and a natural log odds ratio of 1.73 (95% confidence interval, 1.54–1.92) for type 2 diabetes. Within families, the effect of Indigenous American ancestry was −1.51 s.d. (P = 10−8) for height and natural log odds ratio of 5.13 (95% confidence interval, 2.48–7.78) for type 2 diabetes. These effects are supported by between-ancestry differences in trait-increasing allele counts and evidence of selection at trait-associated loci. We found no within-family ancestry effect on educational attainment or other traits despite significant associations at the population level, implying environmental causes or confounding. Overall, this study provides an experimental design to study between-ancestry genetic effects and identifies significant ancestry differences for height, type 2 diabetes and metabolic traits in a genetically diverse population from Mexico City.
SN - 0028-0836
SN - 1476-4687
ER -