rs11044737 (AEBP2): Smoking Behaviors in COPD

Key takeaways

• rs11044737 in the AEBP2 gene was investigated in a genome-wide association study (GWAS) searching for genetic determinants of smoking behaviors in COPD patients.
• The study included 3,441 ever-smoking subjects with at least moderate COPD from four independent cohorts across the United States and Norway.
• The GWAS examined four smoking-related phenotypes: age at smoking initiation, lifetime average cigarettes per day, current cigarettes per day, and smoking cessation.
• Specific association statistics for rs11044737 are not available in the provided study excerpt, limiting what can be stated about this variant in isolation.
• Evidence is preliminary; findings come from a single GWAS conducted in a Caucasian COPD-specific population.

What the research says The variant rs11044737, located in the AEBP2 (Adipocyte Enhancer-Binding Protein 2) gene, was studied in a GWAS of smoking behaviors among COPD patients conducted across four independent cohorts totaling 3,441 ever-smoking subjects with at least GOLD stage II (at least moderate) COPD. The study used HapMap phase II imputation for untyped single nucleotide polymorphisms (SNPs, the class of genetic variants that includes rs11044737) and meta-analyzed results across all cohorts. Study-wide, no SNPs reached a p-value below 10^-6 for cigarettes per day or smoking cessation; the strongest signals for age at smoking initiation reached p=2x10^-7 near chromosome 6p21 and chromosome 2q21.

Reported associations

• Smoking behaviors in COPD (GWAS context): rs11044737 in this locus was included in a GWAS investigating four smoking phenotypes in COPD patients; specific association data for this variant are not reported in the available study text.
• Age at smoking initiation (study-wide top signals): SNPs near the HLA region on chromosome 6p21 and an intergenic region on chromosome 2q21 showed the strongest study-wide associations with age at smoking initiation, both reaching a minimum p-value of 2x10^-7.
• Lifetime average cigarettes per day: Nominally significant associations were found at the CHRNA3/CHRNA5 locus on chromosome 15q25 (p=0.00011 for rs1051730); no variant reached genome-wide significance (p<10^-6) for this trait.
• Current cigarettes per day: The CYP2A6 locus (chromosome 19q13) showed evidence of significant association; no genome-wide significant results were reported for other variants tested.
• Smoking cessation: The DBH (Dopamine Beta-Hydroxylase) candidate SNP rs3025343 showed nominal association with cessation (p=0.015); no variants reached p<10^-6 for this trait.

Evidence quality The source study is a GWAS meta-analysis across four independent COPD cohorts (n=3,441 ever-smoking Caucasian subjects with GOLD stage II or higher COPD). Untyped SNPs were imputed using the HapMap phase II reference panel, and results were meta-analyzed across cohorts, which are standard approaches for multi-cohort GWAS. The restriction to Caucasian subjects with COPD limits generalizability to other ethnicities or to smokers without COPD. No SNPs reached the commonly applied genome-wide significance threshold (p<10^-6) for CPD or smoking cessation phenotypes. The specific p-value, effect size, and replication status of rs11044737 cannot be assessed from the available study excerpt; this represents a substantial limitation for interpreting the evidence base for this variant.

Lifestyle considerations No lifestyle considerations on file for this variant.