Dataset Information

Gene expression in African Americans, Puerto Ricans and Mexican Americans reveals ancestry-specific patterns of genetic architecture.

ABSTRACT: We explored ancestry-related differences in the genetic architecture of whole-blood gene expression using whole-genome and RNA sequencing data from 2,733 African Americans, Puerto Ricans and Mexican Americans. We found that heritability of gene expression significantly increased with greater proportions of African genetic ancestry and decreased with higher proportions of Indigenous American ancestry, reflecting the relationship between heterozygosity and genetic variance. Among heritable protein-coding genes, the prevalence of ancestry-specific expression quantitative trait loci (anc-eQTLs) was 30% in African ancestry and 8% for Indigenous American ancestry segments. Most anc-eQTLs (89%) were driven by population differences in allele frequency. Transcriptome-wide association analyses of multi-ancestry summary statistics for 28 traits identified 79% more gene-trait associations using transcriptome prediction models trained in our admixed population than models trained using data from the Genotype-Tissue Expression project. Our study highlights the importance of measuring gene expression across large and ancestrally diverse populations for enabling new discoveries and reducing disparities.

SUBMITTER: Kachuri L

PROVIDER: S-EPMC10260401 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Gene expression in African Americans, Puerto Ricans and Mexican Americans reveals ancestry-specific patterns of genetic architecture.

Kachuri Linda L Mak Angel C Y ACY Hu Donglei D Eng Celeste C Huntsman Scott S Elhawary Jennifer R JR Gupta Namrata N Gabriel Stacey S Xiao Shujie S Keys Kevin L KL Oni-Orisan Akinyemi A Rodríguez-Santana José R JR LeNoir Michael A MA Borrell Luisa N LN Zaitlen Noah A NA Williams L Keoki LK Gignoux Christopher R CR Burchard Esteban González EG Ziv Elad E

Nature genetics 20230525 6

We explored ancestry-related differences in the genetic architecture of whole-blood gene expression using whole-genome and RNA sequencing data from 2,733 African Americans, Puerto Ricans and Mexican Americans. We found that heritability of gene expression significantly increased with greater proportions of African genetic ancestry and decreased with higher proportions of Indigenous American ancestry, reflecting the relationship between heterozygosity and genetic variance. Among heritable protein ...[more]

PMID: 37231098

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Project description:BackgroundPuerto Ricans and Mexican immigrants are often exposed to multiple types of adversity across their lifetime (e.g., maltreatment, household dysfunction, discrimination) and this exposure can increase the risk for adult mental health problems.PurposeThe objective of this study was to (a) identify subgroups of individuals exposed to unique combinations of childhood adversity and lifetime discrimination among Puerto Ricans and Mexican immigrants, and (b) compare the prevalence of mental health problems across different risk profiles.MethodWe used existing data from the HCHS/SOL Sociocultural Ancillary Study. Participants included Puerto Rican (N = 402) and Mexican adults (N = 1351) born outside but living in the continental U.S.FindingsThrough latent profile analysis, we selected a three-profile solution for Puerto Ricans: (a) Low Exposure (low on all adversity items; 58% of sample), (b) Adverse Childhood Experiences (ACEs) Only (high on ACEs items, average or lower than average on discrimination items; 32%), and (c) Dual Exposure (high on all adversity items; 10%). For Mexicans, we selected a four-profile solution: (a) Low Exposure (52%), (b) ACEs Only (24%), (c) Maltreatment and Discrimination (15%), and (d) Dual Exposure (9%). For Mexicans, we found that the Dual Exposure and the Maltreatment and Discrimination profiles had the highest levels of mental health problems. For Puerto Ricans, the Dual Exposure and ACEs Only profiles had the highest levels of mental health problems, suggesting that Puerto Ricans may be more vulnerable to the effects of childhood adversities as compared to Mexican immigrants. Results from our study indicate that different patterns of adversity exposure are linked to different levels of mental health outcomes, and therefore, may require different intervention dosage. Understanding which groups of individuals are at highest and lowest risk for mental health problems is critical for developing effective, tailored interventions to prevent the negative effects of childhood adversity and discrimination for Latinxs.

Dataset Information

Gene expression in African Americans, Puerto Ricans and Mexican Americans reveals ancestry-specific patterns of genetic architecture.

Publications

Gene expression in African Americans, Puerto Ricans and Mexican Americans reveals ancestry-specific patterns of genetic architecture.

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