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.
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The baseline examination of HCHS/SOL was carried out as a collaborative study supported by contracts from the National Heart, Lung, and Blood Institute (NHLBI) to the University of North Carolina (N01-HC65233), University of Miami (N01-HC65234), Albert Einstein College of Medicine (N01-HC65235), Northwestern University (N01-HC65236), and San Diego State University (N01-HC65237). The following Institutes/Centers/Offices contributed to the first phase of HCHS/SOL through a transfer of funds to the NHLBI: National Institute on Minority Health and Health Disparities, National Institute on Deafness and Other Communication Disorders, National Institute of Dental and Craniofacial Research (NIDCR), National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, NIH Institution-Office of Dietary Supplements. The Genetic Analysis Center at the University of Washington was supported by NHLBI and NIDCR contracts (HHSN268201300005C AM03 and MOD03). Genotyping efforts were supported by NHLBI HSN 26220/20054C, NCATS CTSI grant UL1TR000123, and NIDDK Diabetes Research Center (DRC) grant DK063491. Dr. Hidalgo was supported by an NHLBI Diversity Supplement (HHSN268201300001) and now supported by NHLBI K01 award (K01 HL130609-02), NHLBI PRIDE RISE (R25HL126146). Dr. Qi is supported by a Scientist Development Award (K01HL129892) from the NHLBI. Dr. North is supported by American Heart Association grant 13GRNT16490017 and NIH grant R01DK101855.
The data that support the findings of this study are available from HCHS/SOL but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of HCHS/SOL Steering Committee.
Supplementary information accompanies this paper at https://doi.org/10.1038/s41598-018-35707-7.
Hidalgo, Bertha A.; Sofer, Tamar; Qi, Qibin; Schneiderman, Neil; Chen, Y. -D. Ida; Kaplan, Robert C.; Avilés-Santa, M. Larissa; North, Kari E.; Arnett, Donna K.; Szpiro, Adam; Cai, Jianwen; Yu, Bing; Boerwinkle, Eric; Papanicolaou, George; Laurie, Cathy C.; Rotter, Jerome I.; and Stilp, Adrienne M., "Associations Between SLC16A11 Variants and Diabetes in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)" (2019). Epidemiology and Environmental Health Faculty Publications. 57.