Associations between SLC16A11 variants and diabetes in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

Bertha A. Hidalgo, Tamar Sofer, Qibin Qi, Neil Schneiderman, Y. D.Ida Chen, Robert C. Kaplan, M. Larissa Avilés-Santa, Kari E. North, Donna K. Arnett, Adam Szpiro, Jianwen Cai, Bing Yu, Eric Boerwinkle, George Papanicolaou, Cathy C. Laurie, Jerome I. Rotter, Adrienne M. Stilp

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Abstract

Five sequence variants in SLC16A11 (rs117767867, rs13342692, rs13342232, rs75418188, and rs75493593), which occur in two non-reference haplotypes, were recently shown to be associated with diabetes in Mexicans from the SIGMA consortium. We aimed to determine whether these previous findings would replicate in the HCHS/SOL Mexican origin group and whether genotypic effects were similar in other HCHS/SOL groups. We analyzed these five variants in 2492 diabetes cases and 5236 controls from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), which includes U.S. participants from six diverse background groups (Mainland groups: Mexican, Central American, and South American; and Caribbean groups: Puerto Rican, Cuban, and Dominican). We estimated the SNP-diabetes association in the six groups and in the combined sample. We found that the risk alleles occur in two non-reference haplotypes in HCHS/SOL, as in the SIGMA Mexicans. The haplotype frequencies were very similar between SIGMA Mexicans and the HCHS/SOL Mainland groups, but different in the Caribbean groups. The SLC16A11 sequence variants were significantly associated with risk for diabetes in the Mexican origin group (P = 0.025), replicating the SIGMA findings. However, these variants were not significantly associated with diabetes in a combined analysis of all groups, although the power to detect such effects was 85% (assuming homogeneity of effects among the groups). Additional analyses performed separately in each of the five non-Mexican origin groups were not significant. We also analyzed (1) exclusion of young controls and, (2) SNP by BMI interactions, but neither was significant in the HCHS/SOL data. The previously reported effects of SLC16A11 variants on diabetes in Mexican samples was replicated in a large Mexican-American sample, but these effects were not significant in five non-Mexican Hispanic/Latino groups sampled from U.S. populations. Lack of replication in the HCHS/SOL non-Mexicans, and in the entire HCHS/SOL sample combined may represent underlying genetic heterogeneity. These results indicate a need for future genetic research to consider heterogeneity of the Hispanic/Latino population in the assessment of disease risk, but add to the evidence suggesting SLC16A11 as a potential therapeutic target for type 2 diabetes.

Original languageEnglish (US)
Article number843
JournalScientific reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

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    Hidalgo, B. A., Sofer, T., Qi, Q., Schneiderman, N., Chen, Y. D. I., Kaplan, R. C., Avilés-Santa, M. L., North, K. E., Arnett, D. K., Szpiro, A., Cai, J., Yu, B., Boerwinkle, E., Papanicolaou, G., Laurie, C. C., Rotter, J. I., & Stilp, A. M. (2019). Associations between SLC16A11 variants and diabetes in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Scientific reports, 9(1), [843]. https://doi.org/10.1038/s41598-018-35707-7