rs10152627 (CHD2): Tobacco and Alcohol Use GWAS

Key takeaways

• rs10152627 falls in the CHD2 region and was flagged in a 3.4-million-person multi-ancestry study of tobacco and alcohol use
• The variant reduces CHD2 gene activity in tibial artery tissue and LINC00930 activity in brain cerebellum, per GTEx v11 data
• 99.3% of variants identified in the source study had replication probabilities above 0.99
• Effect sizes were largely consistent across African, American, East Asian, and European ancestry groups

What the research says A multi-ancestry genome-wide association study (GWAS - a method that scans the genome for variants statistically linked to a trait across large populations) involving 3,383,199 individuals identified 2,143 genomic loci containing 3,823 independent variants associated with tobacco and alcohol use behaviors; rs10152627 in the CHD2 region was among the variants identified. The study examined five phenotypes: smoking initiation (n=3,383,199), age at first smoking (n=728,826), cigarettes per day (n=784,353), smoking cessation (n=1,400,535), and drinks per week (n=2,965,643). GTEx v11 eQTL (expression quantitative trait loci - variants that influence how actively a gene is read) data from 953 donors shows the alt allele at this locus is associated with reduced CHD2 expression in tibial artery tissue GTEx Portal.

Reported associations

• Tobacco and alcohol use behaviors: rs10152627 in the CHD2 region was identified in a 3.4-million-person multi-ancestry GWAS spanning smoking initiation, smoking quantity, smoking cessation, and weekly alcohol consumption
• CHD2 expression in tibial artery: The alt allele is associated with reduced CHD2 expression in tibial artery tissue (p=9.5e-6) GTEx Portal
• LINC00930 expression in brain cerebellum: The alt allele is associated with reduced LINC00930 expression in brain cerebellum tissue (p=5.2e-5) GTEx Portal
• ENSG00000288872 expression in testis: The alt allele is associated with reduced expression of ENSG00000288872 in testis tissue (p=5.1e-16) GTEx Portal

Evidence quality The primary GWAS evidence comes from a study of 3,383,199 individuals with representation from four major ancestry groups: African (n=119,589), American (n=286,026), East Asian (n=296,438), and European (n=2,669,029). The authors report that 99.3% of identified sentinel variants had posterior replication probabilities above 0.99, and that the majority of variants showed consistent effect sizes across all ancestry dimensions, strengthening confidence in the locus-level findings. However, the available study text does not report a per-variant effect size (such as an odds ratio or beta coefficient) specifically for rs10152627, which limits precise individual quantification of this variant's contribution. The GTEx eQTL data (953 donors, FDR<0.05) provide mechanistic context rather than disease-outcome evidence; the eQTL effect on ENSG00000288872 in testis is statistically the strongest of the three tissue associations, while the CHD2 effect in tibial artery is more modest in magnitude.

Tissue-specific expression effects

• CHD2: The alt allele is associated with reduced expression in tibial artery tissue GTEx Portal
• LINC00930: The alt allele is associated with reduced expression in brain cerebellum tissue GTEx Portal
• ENSG00000288872: The alt allele is associated with reduced expression in testis tissue GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.