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

TitleAssociations between SLC16A11 variants and diabetes in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).
Publication TypePublication
Year2019
AuthorsHidalgo 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
JournalSci Rep
Volume9
Issue1
Pagination843
Date Published2019 01 29
ISSN2045-2322
KeywordsDiabetes Mellitus, Type 2, Genetic Association Studies, Genetic Predisposition to Disease, Haplotypes, Hispanic Americans, 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.

DOI10.1038/s41598-018-35707-7
Alternate JournalSci Rep
PubMed ID30696834
PubMed Central IDPMC6351621
Grant ListHHSN268201300005C / 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
MS#: 
0376
Manuscript Lead/Corresponding Author Affiliation: 
Affiliated Investigator - Not at HCHS/SOL site
ECI: 
Yes
Manuscript Status: 
Published