Dataset Information

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

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.

SUBMITTER: Hidalgo BA

PROVIDER: S-EPMC6351621 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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

Hidalgo Bertha A BA Sofer Tamar T Qi Qibin Q Schneiderman Neil N Chen Y-D Ida YI Kaplan Robert C RC Avilés-Santa M Larissa ML North Kari E KE Arnett Donna K DK Szpiro Adam A Cai Jianwen J Yu Bing B Boerwinkle Eric E Papanicolaou George G Laurie Cathy C CC Rotter Jerome I JI Stilp Adrienne M AM

Scientific reports 20190129 1

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 Hispa ...[more]

PMID: 30696834

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Project description:BACKGROUND:Sleep apnea and diabetes mellitus (DM) negatively impact cardiovascular health. One important indicator of cardiovascular health is the Ankle-Brachial Index (ABI). Either low ABI or high ABI are signs of peripheral vascular impairment. Impaired vascular health and DM, together, might provoke sleep apnea; however, information regarding these relationships is limited. Therefore, this study aimed to investigate the association between ABI, DM status, and severity of obstructive sleep apnea in people of Hispanic/Latino descent who are diverse in culture, environmental exposures, nativity, socioeconomic status, and disease burden. METHODS:A cross sectional analysis from a multi-center epidemiologic study, Hispanic Community Health Study/Study of Latinos, was utilized and included 3779 participants (mean age 55.32?±?7.67, females 57.9%). The sample was divided into 4 groups based on the American Diabetes Association diagnostic guidelines (no DM or DM), and the ABI status (normal and abnormal). Multiple linear regression analysis was used to determine the association of the four groups and other independent variables with severity of sleep apnea measured by apnea-hypopnea index. Kruskal-Wallis H test was used for comparisons between groups for the apnea-hypopnea index. The significant level was set at 0.01. RESULTS:There were significant differences between groups in the mean of apnea-hypopnea index (P?<?0.001; no DM?+?normal ABI?=?5.42?±?9.66, no DM?+?abnormal ABI?=?7.11?±?11.63, DM?+?normal ABI?=?10.99?±?15.16, DM?+?abnormal ABI?=?12.81?±?17.80). Linear regression showed that DM and abnormal ABI were significantly associated with severe sleep apnea (??=?3.25, P?=?0.001) after controlling for age, sex, BMI, income, education, alcohol use, cigarette use, hypertension or related medication, stroke and statin use. CONCLUSION:These findings suggest that people with DM and abnormal ABI were more likely to have high apnea-hypopnea index compared to the other groups. We observed gradual increasing in the severity of sleep apnea from low abnormality groups to high abnormality groups for Hispanic/Latino. Further work should elucidate the association of DM, abnormal ABI and sleep apnea with longer term outcomes, and replicate this work in different populations.

Project description:ImportanceBoth cardiovascular disease risk and hearing impairment are associated with cognitive dysfunction. However, the combined influence of the 2 risk factors on cognition is not well characterized.ObjectiveTo examine associations between hearing impairment, cardiovascular disease risk, and cognitive function.Design, setting, and participantsThis population-based, prospective cohort, multisite cross-sectional analysis of baseline data collected between 2008 and 2011 as part of the Hispanic Community Health Study/Study of Latinos included 9623 Hispanic or Latino adults aged 45 to 74 years in New York, Chicago, Miami, and San Diego.ExposuresHearing impairment of at least mild severity was defined as the pure tone average of 500, 1000, 2000, and 4000 Hz greater than 25 dB hearing level (dB HL) in the better ear. Our measure of cardiovascular disease risk was a latent class variable derived from body mass index, ankle-brachial index, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, fasting blood glucose, and the Framingham Cardiovascular Risk score.Main outcomes and measuresResults on Brief-Spanish English Verbal Learning Test (episodic learning and memory), and Word Fluency (verbal fluency), and Digit Symbol Subtest (processing speed/executive functioning), and a cognitive composite of the mentioned tests (overall cognition).ResultsParticipants (N = 9180) were 54.4% female and age 56.5 years on average. Hearing impairment was associated with poorer performance on all cognitive measures (global cognition: unstandardized β, -0.11; 95% CI, -0.16 to 0.07). Cardiovascular grouping (healthy, typical, high cardiovascular disease risk, and hyperglycemia) did not attenuate the associations between hearing impairment and cognition (global cognition: unstandardized β, -0.11; 95% CI, -0.15 to -0.06). However, cardiovascular grouping interacted with hearing impairment such that hyperglycemia in the context of hearing impairment exacerbated poor performance on learning and memory tasks (F3 = 3.70 and F3 = 2.92, respectively).Conclusions and relevanceThe findings of this cohort study suggest that hearing impairment increases the likelihood that individuals with excessively high glucose perform poorly on learning and memory tasks. Further research is needed to specify the mechanisms by which cardiovascular disease risk and hearing impairment are collectively associated with cognition.

Dataset Information

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

Publications

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

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