Genome-wide association study of nicotine dependence in American populations: identification of novel risk loci in both African-Americans and European-Americans

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#black-or-african-american #databases-genetic #genetic-predisposition-to-disease #genome-wide-association-study #genotyping-techniques

Genome-wide association study of nicotine dependence in American populations: identification of novel risk loci in both African-Americans and European-Americans

Gelernter et al., 2015 | Biol Psychiatry | Meta Analysis

Citation

Gelernter Joel, Kranzler Henry R, ... Farrer Lindsay A. Genome-wide association study of nicotine dependence in American populations: identification of novel risk loci in both African-Americans and European-Americans. Biol Psychiatry. 2015-Mar-01;77(5):493-503. doi:10.1016/j.biopsych.2014.08.025

Abstract

BACKGROUND: We report a genome-wide association study (GWAS) of nicotine dependence defined on the basis of scores on the Fagerström Test for Nicotine Dependence in European-American (EA) and African-American (AA) populations. METHODS: Our sample, from the one used in our previous GWAS, included only subjects who had smoked >100 cigarettes lifetime (2114 EA and 2602 AA subjects) and an additional 927 AA and 2003 EA subjects from the Study of Addiction: Genetics and Environment project [via the database of Genotypes and Phenotypes (dbGAP)]. GWAS analysis considered Fagerström Test for Nicotine Dependence score as an ordinal trait, separately in each population and sample and by combining the results in meta-analysis. We also conducted analyses that were adjusted for other substance use disorder criteria in a single nucleotide polymorphism (SNP) subset. RESULTS: In EAs, one chromosome 7 intergenic region was genome-wide significant (GWS): rs13225753, p = 3.48 × 10(-8) (adjusted). In AAs, GWS associations were observed at numerous SNPs mapped to a region on chromosome 14 of >305,000 base pairs (minimal p = 4.74 × 10(-10)). Two chromosome 8 regions were associated: p = 4.45 × 10(-8) at DLC1 SNP rs289519 (unadjusted) and p = 1.10 × 10(-9) at rs6996964 (adjusted for other substances), located between CSGALNACT1 and INTS10. No GWS associations were observed at the chromosome 15 nicotinic receptor gene cluster (CHRNA5-CHRNA3-CHRNB4) previously associated with nicotine dependence and smoking quantity traits. TSNAX-DISC1 SNP rs821722 (p = 1.46 × 10(-7)) was the most significant result with substantial contributions from both populations; we previously identified DISC1 associations with opioid dependence. Pathway analysis identified association with nitric oxide synthase and adenosine monophosphate-activated protein kinase pathways in EAs. CONCLUSIONS: The key risk loci identified, which require replication, offer novel insights into nicotine dependence biology.

Key Findings

In EAs, one chromosome 7 intergenic region was genome-wide significant (GWS): rs13225753, p = 3.48 × 10(-8) (adjusted). In AAs, GWS associations were observed at numerous SNPs mapped to a region on chromosome 14 of >305,000 base pairs (minimal p = 4.74 × 10(-10)). Two chromosome 8 regions were associated: p = 4.45 × 10(-8) at DLC1 SNP rs289519 (unadjusted) and p = 1.10 × 10(-9) at rs6996964 (adjusted for other substances), located between CSGALNACT1 and INTS10. No GWS associations were observed

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population See abstract
Sample Size See abstract
Age Range See abstract
Condition See abstract

MeSH Terms

  • Black or African American
  • Databases, Genetic
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Genotyping Techniques
  • Humans
  • Polymorphism, Single Nucleotide
  • Severity of Illness Index
  • Smoking
  • Tobacco Use Disorder
  • United States
  • White People

Evidence Classification

  • Level: Meta Analysis
  • Publication Types: Comparative Study, Journal Article, Meta-Analysis, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.
  • Vertical: niacin

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09