Genomic Consortium Diversifies Data, Explores Genomics of Body Measurements

By Allison Proffitt

April 19, 2022 | Genomic studies can benefit from leveraging diverse ancestries to make new discoveries about health and disease, write the authors of a new paper published in Human Genetics and Genomics Advances (DOI: 10.1016/j.xhgg.2022.100099). They have launched a consortium focused on the genetics of Hispanic and Latin American populations.

Lindsay Fernández-Rhodes, assistant professor of biobehavioral health at Penn State, and Mariaelisa Graff, associate professor of epidemiology at University of North Carolina at Chapel Hill, jointly led the work, which showed that increasing the diversity of genomic samples can improve researchers’ ability to identify important genetic insights into growth, development, and body fat distribution. 

Hispanic/Latino populations are extremely diverse, Fernández-Rhodes explains. “Culturally, linguistically, geographically—especially in the United States where they represent a wide array of heritages, the diversity is remarkable,” she says. Individuals self-identifying as Hispanic or Latino are also quite diverse ancestrally, representing ancestries from the Americas, Europe, Africa, and even Asia. The result is a rich sample representing significant genetic diversity, as compared to previous European-based genome-wide association studies (GWAS), but also significant genetic diversity within the group itself.

Such diversity is crucial to advancing precision medicine, Fernández-Rhodes says. “We cannot treat people with precision if we do not have the relevant data. Previous large-scale genomic studies have largely overlooked Hispanic/Latino people. Since the United States is becoming increasingly diverse, our ability to provide appropriate medical treatment will suffer if the gaps in our genomic data are not addressed,” she noted in a press release about the work.  

Fernández-Rhodes and the team were joined by more than 100 researchers from around the world to form the Hispanic/Latino Anthropometry Consortium (HISLA Consortium), which was created for this study. The HISLA Consortium is comprised of 27 studies/consortia of adult participants. HISLA stage 1 includes 17 studies and one consortium (Consortium for the Analysis of the Diversity and Evolution of Latin America [CANDELA]) collectively representing up to 59,771 adults, Brazil, Chile, Colombia, Mexico, Peru, or the US with self-reported heritage from the Americas. HISLA stage 2 includes 9 studies with up to 10,538 adults from across Latin America or from the US of Hispanic/Latino heritage.

Body Genetics

Fernández-Rhodes and Graff led the GWAS analysis of more than 70,000 Hispanic/Latino individuals focusing on anthropometric traits: body mass index (BMI), height, and waist-to-hip ratio. BMI, a ratio of weight to height squared, is the most common assessment of obesity used by physicians; waist-to-hip ratio indicates where on their bodies people are carrying excess weight.

“To date, no large-scale GWAS of anthropometric traits has been conducted among Hispanic/Latino populations,” the authors wrote in the paper. “We therefore performed a large-scale genomic study of multiple anthropometric traits, including BMI, height, and waist-to-hip ratio adjusted for BMI (WHRadjBMI), in Hispanic/Latino populations to describe what may be novel loci, or new signals in established loci, for this population.”

The GWAS analysis revealed 42 previously unidentified regions of the human genome related to BMI, height, and waist-to-hip ratio. These traits have been examined in previous genomic studies, but the unique ancestry and experiences of Hispanic/Latino people made the regions easier to identify using the consortium's data. 

“We found regions of the genome that are seen in appreciable frequency in Hispanic/Latinos, but we also see that these findings are generally relevant across the globe, meaning for all human populations,” Fernández-Rhodes says. The 42 regions identified here are likely relevant to all humans, but the HISLA Consortium’s uniquely diverse sample made them easier to identify.”

“Most of the studies previously done are of European descent samples, and the sample sizes are very large. They contain hundreds of thousands of people and millions of analyses. Our sample was comparatively smaller, but far richer with respect to its diversity. It’s a kind of a proof-of-concept that by improving diversity and inclusion in our genomic studies we can do a better job of understanding our human biology,” Fernández-Rhodes explains.  

The newly identified regions of the genome may help scientists understand how people grow, and develop. They may also aid researchers in predicting individuals at risk for develop obesity.

“Genomic prediction measures—often called genetic risk scores—rely on estimates from large studies like ours and previously there were no Hispanic/Latino-specific studies with estimates publicly available for researchers to use,” Fernández-Rhodes says. “It is possible that by building this consortium we’re going to enable more equitable risk prediction, and better precision medicine in the future.”

These types of diverse population studies will be increasingly valuable to our understanding of genetics in the future, the authors write. “Large-scale analyses of diverse populations hold great potential for advancing the field of genetic epidemiology.”

While a second study isn’t yet underway, Fernández-Rhodes expects the HISLA Consortium will have longevity and likely shift to exploring cardiovascular disease outcomes in the near future. “We’ve already assembled this group of 100-plus wonderful researchers from across the globe and we look forward to seeing this through to the next phase.”