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.

墨西哥城前瞻性研究是二十年前从墨西哥城科约阿坎和伊斯塔帕拉帕市区招募的超过 150,000 名成年人的前瞻性队列¹ 。在这里，我们生成了所有个体的基因型和外显子组测序数据以及 9,950 名选定个体的全基因组测序数据。我们描述了个体之间祖先组成的高度相关性和显着异质性。大多数测序个体都混有美洲原住民、欧洲原住民和非洲原住民血统，其中还广泛混有墨西哥中部、南部和东南部原住民的血统。与非洲和欧洲起源的片段相比，墨西哥本土基因组片段的编码变异水平较低，但纯合性功能丧失变异过多。我们估计了 1.42 亿个基因组变异的血统特异性等位基因频率，外显子组变异的墨西哥土著血统的有效样本量为 91,856 个，所有这些都可以通过公共浏览器获得。利用全基因组测序，我们开发了一个插补参考组，该组在具有高比例中部、南部和东南部墨西哥原住民血统的个体的常见变异方面优于现有的组。我们的工作说明了不同人群中遗传学研究的价值，并为墨西哥和美国（西班牙裔/拉丁裔人口主要为墨西哥血统）未来的遗传学研究提供了基础插补和等位基因频率资源。