Genomic

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Nicotine Dependence GWAS Meta-Analysis


ABSTRACT:

Nicotine dependence reduces the likelihood of quitting smoking and predicts withdrawal severity, treatment response, and smoking-related health outcomes. Nicotine dependence is a heritable trait (heritability estimates up to 75%), and prior genome-wide association study (GWAS) analyses have firmly established associations with DNA sequence variants in nicotine acetylcholine receptor genes on chromosome 15q25 and at other loci. In this GWAS meta-analysis, 15 independent studies were assembled for a total of 38,602 regular smokers (28,677 Europeans/European Americans and 9,925 African Americans) with nicotine dependence defined by the Fagerström Test for Nicotine Dependence (FTND). FTND scores, which range from 0 (no dependence) to 10 (highest dependence level), were used to categorize nicotine dependence as mild (scores 0-3), moderate (scores 4-6), or severe (scores 7-10). Two of the 15 studies additionally included low-intensity smokers who reported cigarettes per day as <10 but had no data available on the other FTND items and were defined as mildly dependent, given the high concordance rates between these FTND and CPD categories and minimal phenotype misclassification. The cross-ancestry GWAS meta-analysis tested nearly 18 million genotyped and 1000 Genomes-imputed SNPs/indels for association with mild/moderate/severe dependence. The well-known chromosome 15q25 locus was reconfirmed, and a novel chromosome 20q11 locus spanning the DNA (cytosine-5-)-methyltransferase 3 beta (DNMT3B) gene was identified at genome-wide significance. Genome-wide results for the cross-ancestry and ancestry-specific GWAS meta-analyses are provided.

PROVIDER: phs001532 | dbGaP |

REPOSITORIES: dbGaP

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