Abstract
Admixture mapping can be used to detect genetic association regions in admixed populations, such as Hispanics/Latinos, by estimating associations between local ancestry allele counts and the trait of interest. We performed admixture mapping of the blood pressure traits systolic and diastolic blood pressure (SBP, DBP), mean arterial pressure (MAP), and pulse pressure (PP), in a dataset of 12,116 participants from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Hispanics/Latinos have three predominant ancestral populations (European, African, and Amerindian), for each of which we separately tested local ancestry intervals across the genome. We identified four regions that were significantly associated with a blood pressure trait at the genome-wide admixture mapping level. A 6p21.31 Amerindian ancestry association region has multiple known associations, but none explained the admixture mapping signal. We identified variants that completely explained this signal. One of these variants had p-values of 0.02 (MAP) and 0.04 (SBP) in replication testing in Pima Indians. A 11q13.4 Amerindian ancestry association region spans a variant that was previously reported (p-value = 0.001) in a targeted association study of Blood Pressure (BP) traits and variants in the vitamin D pathway. There was no replication evidence supporting an association in the identified 17q25.3 Amerindian ancestry association region. For a region on 6p12.3, associated with African ancestry, we did not identify any candidate variants driving the association. It may be driven by rare variants. Whole genome sequence data may be necessary to fine map these association signals, which may contribute to disparities in BP traits between diverse populations.
Highlights
Cardiovascular disease is a major cause of death in the United States and worldwide
Admixture mapping can be more powerful than association testing [16] in the sense that a statistically significant association may be detected in admixture mapping but not in association mapping, in some settings: (1) when a genotype is not typed or imputed in the genotyping platform, but is found within and LAI—this is especially true for rare variants that are typed less (or are filtered out due to unreliable statistical properties; (2) there are multiple associated variants within an LAI; and (3) the number of LAIs is smaller than the number of genotypes tested in a genome-wide association studies (GWASs), leading to reduced multiple testing burden
While the distributions of age, sex, and Body Mass Index were similar across Mainland and Caribbean participants, hypertension was more prevalent in the Caribbeans, and SBP, DBP, mean arterial pressure (MAP), and pulse pressure (PP) were somewhat higher
Summary
Cardiovascular disease is a major cause of death in the United States and worldwide. Blood pressure is a strong risk factor for cardiovascular disease and has a known genetic component. [11,12,13,14] GWAS tests the association of each “dose” of genotyped or imputed variant with a trait of interest In populations such as Hispanics/Latinos who are an admixture of European, African, and Amerindian ancestries, association studies can be performed using an admixture mapping approach, where one tests the association of local ancestry counts in genomic intervals spanning tens, or even hundreds of thousands of base pairs, and the trait. Admixture mapping is especially useful for analysis of blood pressure traits, because their distribution differ between ancestral groups. We performed admixture mapping of quantitative blood pressure traits, SBP, DBP, MAP, and PP in a population of United States (U.S.) Hispanics/Latinos from the HCHS/SOL. We assessed replication of four Amerindian variant associations in a population of Southwest American Indians
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