Advancements in genetic research by the Hispanic Community Health Study/Study of Latinos: A 10-year retrospective review

Abstract

The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) is a multicenter, longitudinal cohort study designed to evaluate environmental, lifestyle, and genetic risk factors as they relate to cardiometabolic and other chronic diseases among Hispanic/Latino populations in the United States. Since the study's inception in 2008, as a result of the study's robust genetic measures, HCHS/SOL has facilitated major contributions to the field of genetic research. This 10-year retrospective review highlights the major findings for genotype-phenotype relationships and advancements in statistical methods owing to the HCHS/SOL. Furthermore, we discuss the ethical and societal challenges of genetic research, especially among Hispanic/Latino adults in the United States. Continued genetic research, ancillary study expansion, and consortia collaboration through HCHS/SOL will further drive knowledge and advancements in human genetics research.

Figure 1

Availability of genetic data of HCHS/SOL participants (A) Patterns of consent for participation in genetic studies in HCHS/SOL Visits 1 and 2. (B) Genotyping efforts in HCHS/SOL. Initially, 12,803 individuals who were genotyped via the OLa project. Later, individuals were genotyped via the PAGE study together with individuals from other studies. Both OLa and PAGE genotyped data were imputed to the 1000 Genomes phase 3 reference panel and later to TOPMed reference panel. Finally, most of the genotyped individuals and additional individuals were sequenced (WGS) via the NHLBI’s TOPMed and the NHGRI’s CCDG projects. TOPMed and CCDG genotyped and performed joint allele calling of participants from many parent studies. As of 2024, there are 14,126 HCHS/SOL individuals with genome-wide genetic data across the three levels of informed consent: allowing genetic data to be used only by HCHS/SOL investigators or their collaborators (“Only SOL”), allowing genetic data to be used only by researchers from nonprofit organizations (“Non profit”), or allowing genetic data to be used also by researchers from for-profit organizations (“For profit”). The first 2,694 Visit 1 participants who consented via the first version of the informed consent form (“Consent form 1”) were not genotyped initially. CCDG, Centers for Common Disease Genomics; IC, informed consent; NHGRI, National Human Genome Research Institute; NHLBI, National Heart, Lung, and Blood Institute; OLa, omics in Latinos; PAGE, Population Architecture using Genomics; SOL, (Hispanic Community Health Study) Study of Latinos; TOPMed, trans-omics in precision medicine.

Figure 2

Characteristics of HCHS/SOL participants who consented to genetic analyses (N = 14,042) Characteristics are based on the baseline visit are stratified by self-reported Hispanic/Latino background. The figure shows age distributions and lists the sample size, percentage of female individuals, mean, standard deviation, and range of age, percentage of participants with income less than or greater than or equal to 30,000 USD per household per year, percentages of participant by education categories (no high school diploma or GED, at most a high school diploma or GED, greater than high school [or GED] education), and percentage of participants who were born in the 50 US states/DC (US born). Sex was assigned in visit 1 and is presumed to be the sex assigned at birth.

Figure 3

Self-reported Hispanic/Latino background, race, and ancestry in HCHS/SOL The figure is limited to 10,471 individuals with non-missing self-reported Hispanic/Latino background and race, inferred global genetic ancestry proportions, and who consented for genetic data sharing with either HCHS/SOL investigators or other nonprofit or for-profit researchers. Left: proportions of inferred African, Amerindian, and European continental ancestries for HCHS/SOL participant of each Hispanic/Latino background (Dominican n = 962; Central American n = 1,146; Cuban n = 1,768; Mexican N = 3,753; Puerto Rican n = 1,825; South American n = 793; More than one/Other n = 314). This figure demonstrates there are background-specific patterns of global genetic ancestries, which are known to be due to demographic history. Top right: values of the first and second genetic PCs, with points colored by self-reported Hispanic/Latino background. PC1 explains 2.55% and PC2 explains 1.12% of the genetic variance in the dataset. This figure demonstrates that Hispanic/Latino backgrounds tend to cluster together on PC space. Bottom right: distribution of inferred proportions of genetic ancestry by categories of self-reported race (American Indian/AK native n = 405; Asian n = 23; HW native/PC islander n = 25; Black n = 359; White n = 4,055; Multi-racial n = 1,790; Unknown/NR n = 112, Refused n = 3,702). This figure demonstrates that self-reported race is only weakly related to patterns of admixture of ancestral population ancestries in HCHS/SOL Hispanics/Latinos. AK, Alaska; HCHS/SOL, the Hispanic Community Health Study/Study of Latinos; HW, Hawaii; NR, non-response; Pac, Pacific; PC, principal component.

Figure 4

Cumulative number and type of human genetic studies published from HCHS/SOL since 2014

Figure 5

Heatmap depicting genetic epidemiological study types and studied health outcomes conducted using HCHS/SOL data White tiles correspond to no publications in the category. AM, admixture mapping; FM, fine mapping; GWAS, genome-wide association study; GxE, Gene-by-environment interaction study; MR, Mendelian randomization; PRS, Polygenic Risk Score; Met, Metabolomics.