Dataset Information

Genome-Wide Association Study of Heavy Smoking and Daily/Nondaily Smoking in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

ABSTRACT: Introduction:Genetic variants associated with nicotine dependence have previously been identified, primarily in European-ancestry populations. No genome-wide association studies (GWAS) have been reported for smoking behaviors in Hispanics/Latinos in the United States and Latin America, who are of mixed ancestry with European, African, and American Indigenous components. Methods:We examined genetic associations with smoking behaviors in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) (N = 12 741 with smoking data, 5119 ever-smokers), using ~2.3 million genotyped variants imputed to the 1000 Genomes Project phase 3. Mixed logistic regression models accounted for population structure, sampling, relatedness, sex, and age. Results:The known region of CHRNA5, which encodes the ?5 cholinergic nicotinic receptor subunit, was associated with heavy smoking at genome-wide significance (p ? 5 × 10-8) in a comparison of 1929 ever-smokers reporting cigarettes per day (CPD) > 10 versus 3156 reporting CPD ? 10. The functional variant rs16969968 in CHRNA5 had a p value of 2.20 × 10-7 and odds ratio (OR) of 1.32 for the minor allele (A); its minor allele frequency was 0.22 overall and similar across Hispanic/Latino background groups (Central American = 0.17; South American = 0.19; Mexican = 0.18; Puerto Rican = 0.22; Cuban = 0.29; Dominican = 0.19). CHRNA4 on chromosome 20 attained p < 10-4, supporting prior findings in non-Hispanics. For nondaily smoking, which is prevalent in Hispanic/Latino smokers, compared to daily smoking, loci on chromosomes 2 and 4 achieved genome-wide significance; replication attempts were limited by small Hispanic/Latino sample sizes. Conclusions:Associations of nicotinic receptor gene variants with smoking, first reported in non-Hispanic European-ancestry populations, generalized to Hispanics/Latinos despite different patterns of smoking behavior. Implications:We conducted the first large-scale genome-wide association study (GWAS) of smoking behavior in a US Hispanic/Latino cohort, and the first GWAS of daily/nondaily smoking in any population. Results show that the region of the nicotinic receptor subunit gene CHRNA5, which in non-Hispanic European-ancestry smokers has been associated with heavy smoking as well as cessation and treatment efficacy, is also significantly associated with heavy smoking in this Hispanic/Latino cohort. The results are an important addition to understanding the impact of genetic variants in understudied Hispanic/Latino smokers.

SUBMITTER: Saccone NL

PROVIDER: S-EPMC5896462 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Genome-Wide Association Study of Heavy Smoking and Daily/Nondaily Smoking in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

Saccone Nancy L NL Emery Leslie S LS Sofer Tamar T Gogarten Stephanie M SM Becker Diane M DM Bottinger Erwin P EP Chen Li-Shiun LS Culverhouse Robert C RC Duan Weimin W Hancock Dana B DB Hosgood H Dean HD Johnson Eric O EO Loos Ruth J F RJF Louie Tin T Papanicolaou George G Perreira Krista M KM Rodriquez Erik J EJ Schurmann Claudia C Stilp Adrienne M AM Szpiro Adam A AA Talavera Gregory A GA Taylor Kent D KD Thrasher James F JF Yanek Lisa R LR Laurie Cathy C CC Pérez-Stable Eliseo J EJ Bierut Laura J LJ Kaplan Robert C RC

Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco 20180301 4

<h4>Introduction</h4>Genetic variants associated with nicotine dependence have previously been identified, primarily in European-ancestry populations. No genome-wide association studies (GWAS) have been reported for smoking behaviors in Hispanics/Latinos in the United States and Latin America, who are of mixed ancestry with European, African, and American Indigenous components.<h4>Methods</h4>We examined genetic associations with smoking behaviors in the Hispanic Community Health Study/Study of ...[more]

PMID: 28520984

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Project description: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.

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

Genome-Wide Association Study of Heavy Smoking and Daily/Nondaily Smoking in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

Publications

Genome-Wide Association Study of Heavy Smoking and Daily/Nondaily Smoking in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

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