# Genotyping, sequencing and analysis of 140,000 adults from Mexico City

## TL;DR

This study provides genetic data from 150,000 adults in Mexico City, revealing ancestry diversity and creating resources for future genetic research in Mexican and Hispanic/Latino populations.

## Contribution

The study generates a large-scale genetic dataset and a new imputation reference panel for Indigenous Mexican ancestry.

## Key findings

- The study found high relatedness and ancestry heterogeneity among participants with significant Indigenous Mexican, European, and African ancestry.
- Indigenous Mexican genomic segments showed lower coding variation and more homozygous loss-of-function variants compared to African and European segments.
- A new imputation reference panel was developed that outperforms existing panels for individuals with high Indigenous Mexican ancestry.

## Abstract

The Mexico City Prospective Study is a prospective cohort of more than 150,000 adults recruited two decades ago from the urban districts of Coyoacán and Iztapalapa in Mexico City1. Here we generated genotype and exome-sequencing data for all individuals and whole-genome sequencing data for 9,950 selected individuals. We describe high levels of relatedness and substantial heterogeneity in ancestry composition across individuals. Most sequenced individuals had admixed Indigenous American, European and African ancestry, with extensive admixture from Indigenous populations in central, southern and southeastern Mexico. Indigenous Mexican segments of the genome had lower levels of coding variation but an excess of homozygous loss-of-function variants compared with segments of African and European origin. We estimated ancestry-specific allele frequencies at 142 million genomic variants, with an effective sample size of 91,856 for Indigenous Mexican ancestry at exome variants, all available through a public browser. Using whole-genome sequencing, we developed an imputation reference panel that outperforms existing panels at common variants in individuals with high proportions of central, southern and southeastern Indigenous Mexican ancestry. Our work illustrates the value of genetic studies in diverse populations and provides foundational imputation and allele frequency resources for future genetic studies in Mexico and in the United States, where the Hispanic/Latino population is predominantly of Mexican descent.

Genotype and exome sequencing of 150,000 participants and whole-genome sequencing of 9,950 selected individuals recruited into the Mexico City Prospective Study constitute a valuable, publicly available resource of non-European sequencing data.