Title | Associations between SLC16A11 variants and diabetes in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). |
Publication Type | Publication |
Year | 2019 |
Authors | Hidalgo BA, Sofer T, Qi Q, Schneiderman N, Chen Y-DIda, Kaplan RC, M Avilés-Santa L, North KE, Arnett DK, Szpiro A, Cai J, Yu B, Boerwinkle E, Papanicolaou G, Laurie CC, Rotter JI, Stilp AM |
Journal | Sci Rep |
Volume | 9 |
Issue | 1 |
Pagination | 843 |
Date Published | 2019 Jan 29 |
ISSN | 2045-2322 |
Keywords | Diabetes Mellitus, Type 2, Genetic Association Studies, Genetic Predisposition to Disease, Haplotypes, Hispanic or Latino, Humans, Monocarboxylic Acid Transporters, Polymorphism, Single Nucleotide, United States |
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. |
DOI | 10.1038/s41598-018-35707-7 |
Alternate Journal | Sci Rep |
PubMed ID | 30696834 |
PubMed Central ID | PMC6351621 |
Grant List | HHSN268201300005C / HL / NHLBI NIH HHS / United States HHSN268201300001C / HL / NHLBI NIH HHS / United States R25 HL126146 / HL / NHLBI NIH HHS / United States N01HC65236 / HL / NHLBI NIH HHS / United States N01HC65234 / HL / NHLBI NIH HHS / United States R01 DK101855 / DK / NIDDK NIH HHS / United States P30 DK020541 / DK / NIDDK NIH HHS / United States M01 RR000032 / RR / NCRR NIH HHS / United States K01 HL130609 / HL / NHLBI NIH HHS / United States P30 DK079626 / DK / NIDDK NIH HHS / United States N01HC65235 / HL / NHLBI NIH HHS / United States P30 DK063491 / DK / NIDDK NIH HHS / United States N01HC65233 / HL / NHLBI NIH HHS / United States K01 HL129892 / HL / NHLBI NIH HHS / United States P30 DK111022 / DK / NIDDK NIH HHS / United States N01HC65237 / HL / NHLBI NIH HHS / United States U54 TR000123 / TR / NCATS NIH HHS / United States |
Associations between SLC16A11 variants and diabetes in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).
MS#:
0376
ECI:
Yes
Manuscript Status:
Published