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

Research output: Contribution to journalArticle

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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Hispanic Americans
Health
Haplotypes
Single Nucleotide Polymorphism
Genetic Research
Genetic Heterogeneity

ASJC Scopus subject areas

  • General

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

In: Scientific Reports, Vol. 9, No. 1, 843, 01.12.2019.

Research output: Contribution to journalArticle

Hidalgo, BA, Sofer, T, Qi, Q, Schneiderman, N, Chen, YDI, Kaplan, RC, Avilés-Santa, ML, North, KE, Arnett, DK, Szpiro, A, Cai, J, Yu, B, Boerwinkle, E, Papanicolaou, G, Laurie, CC, Rotter, JI & Stilp, AM 2019, 'Associations between SLC16A11 variants and diabetes in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)', Scientific Reports, vol. 9, no. 1, 843. 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. ; Stilp, Adrienne M. / Associations between SLC16A11 variants and diabetes in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). In: Scientific Reports. 2019 ; Vol. 9, No. 1.
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AU - Hidalgo, Bertha A.

AU - Sofer, Tamar

AU - Qi, Qibin

AU - Schneiderman, Neil

AU - Chen, Y. D.Ida

AU - Kaplan, Robert C.

AU - Avilés-Santa, M. Larissa

AU - North, Kari E.

AU - Arnett, Donna K.

AU - Szpiro, Adam

AU - Cai, Jianwen

AU - Yu, Bing

AU - Boerwinkle, Eric

AU - Papanicolaou, George

AU - Laurie, Cathy C.

AU - Rotter, Jerome I.

AU - Stilp, Adrienne M.

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N2 - 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.

AB - 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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