Nicotine Dependence GWAS Meta-Analysis

Cigarette smoking is the leading cause of preventable morbidity and mortality. Knowledge is evolving on genetics underlying initiation, regular smoking, nicotine dependence (ND), and cessation. We performed a genome-wide association study using the Fagerström Test for ND (FTND) in 58,000 smokers of European or African ancestry. Five genome-wide significant loci, including two novel loci MAGI2/GNAI1 (rs2714700) and TENM2 (rs1862416) were identified, and loci reported for other smoking traits were extended to ND. Using the heaviness of smoking index (HSI) in the UK Biobank (N=33,791), rs2714700 was consistently associated, but rs1862416 was not associated, likely reflecting ND features not captured by the HSI. Both variants were cis-eQTLs (rs2714700 for MAGI2-AS3 in hippocampus, rs1862416 for TENM2 in lung), and expression of genes spanning ND-associated variants was enriched in cerebellum. SNP-based heritability of ND was 8.6%, and ND was genetically correlated with 13 other smoking traits (rg=0.40-0.95) and co-morbid diseases. Our results emphasize the FTND as a composite phenotype that expands genetic knowledge of smoking, including loci specific to ND.]]>
We performed a genome-wide association meta-analyses to identify loci associated with nicotine dependence, by combining results from 15 cohorts with Fagerstrom Test for Nicotine Dependence data used to define mild, moderate, and severe dependence among ever smokers. Cohorts were genotyped on various genome-wide platforms, and following quality control, the genotype data were used to carry out 1000 Genomes imputation. We used linear regression to test the imputed dosages for association with nicotine dependence, adjusted for age, sex, ancestry principal components, and cohort-specific covariates (as needed). Additional adjustment for family structure was made in the studies with relatives included. Here, we report the results from the African American-specific meta-analysis that included total N=9,925 participants from 8 cohorts.We performed genome-wide association meta-analyses to identify genetic loci associated with nicotine dependence, by combining results from 15 cohorts from the US and Europe with Fagerstrom Test for Nicotine Dependence data used to define mild, moderate, and severe dependence among ever smokers. Cohorts were genotyped on various platforms, and following quality control, the genotype data were used to carry out 1000 Genomes imputation. We used linear regression to test the imputed dosages for association with nicotine dependence, adjusted for age, sex, ancestry principal components, and cohort-specific covariates (as needed). Additional adjustment for family structure was made in the studies with relatives included. Here, we report the results from the European ancestry-specific meta-analysis that included total N=28,677 participants from 13 cohorts.We performed a genome-wide association meta-analyses to identify loci associated with nicotine dependence, by combining results from 15 cohorts with Fagerstrom Test for Nicotine Dependence data used to define mild, moderate, and severe dependence among ever smokers. Cohorts were genotyped on various genome-wide platforms, and following quality control, the genotype data were used to carry out 1000 Genomes imputation. We used linear regression to test the imputed dosages for association with nicotine dependence, adjusted for age, sex, ancestry principal components, and cohort-specific covariates (as needed). Additional adjustment for family structure was made in the studies with relatives included. Here, we report the results from the cross-ancestry meta-analysis that included total N=38,602 European ancestry and African American participants from the 15 cohorts.We performed a genome-wide association meta-analyses to identify loci associated with nicotine dependence, by combining results from 25 cohorts with Fagerström Test for Nicotine Dependence data used to define mild, moderate, and severe dependence among ever smokers. Cohorts were genotyped on various genome-wide platforms, and following quality control, the genotype data were used to carry out 1000 Genomes imputation. We used linear regression to test the imputed dosages for association with nicotine dependence, adjusted for age, sex, ancestry principal components, and cohort-specific covariates (as needed). Additional adjustment for family structure was made in the studies with relatives included. Here, we report the results from the African American-specific meta-analysis that included total N=11,787 participants from 11 cohorts.We performed a genome-wide association meta-analyses to identify loci associated with nicotine dependence, by combining results from 25 cohorts with Fagerström Test for Nicotine Dependence data used to define mild, moderate, and severe dependence among ever smokers. Cohorts were genotyped on various genome-wide platforms, and following quality control, the genotype data were used to carry out 1000 Genomes imputation. We used linear regression to test the imputed dosages for association with nicotine dependence, adjusted for age, sex, ancestry principal components, and cohort-specific covariates (as needed). Additional adjustment for family structure was made in the studies with relatives included. Here, we report the results from the cross-ancestry meta-analysis that included total N=58,000 European ancestry and African American participants from the 25 cohorts.We performed genome-wide association meta-analyses to identify genetic loci associated with nicotine dependence, by combining results from 23 cohorts from the US and Europe with Fagerström Test for Nicotine Dependence data used to define mild, moderate, and severe dependence among ever smokers. Cohorts were genotyped on various platforms, and following quality control, the genotype data were used to carry out 1000 Genomes imputation. We used linear regression to test the imputed dosages for association with nicotine dependence, adjusted for age, sex, ancestry principal components, and cohort-specific covariates (as needed). Additional adjustment for family structure was made in the studies with relatives included. Here, we report the results from the European ancestry-specific meta-analysis that included total N=46,213 participants from 20 cohorts.To be included in this nicotine dependence study, a study sample had to have genome-wide SNP genotypes and Fagerström Test for Nicotine Dependence (FTND) phenotype data collected among current and/or former smokers. Study samples included European/European American and African American participants.]]>