rs1174749 (POM121L12): Tobacco and Alcohol Use Variant

Key takeaways

• rs1174749, located near POM121L12 and HAUS6P1, was flagged in one of the largest genetic studies of smoking and drinking ever conducted, covering about 3.4 million people worldwide.
• The study included roughly 21% non-European participants, improving genetic mapping across diverse ancestry groups.
• Most of the 3,823 associated variants identified showed similar effect sizes regardless of the participant's ancestry background.
• Polygenic risk scores built from predominantly European data showed reduced accuracy in other ancestry groups, a key limitation the researchers explicitly noted.

What the research says A large multi-ancestry genome-wide association study (GWAS - a simultaneous scan of hundreds of thousands to millions of genetic positions across the genome) involving approximately 3.4 million individuals from 60 cohorts identified rs1174749 in the POM121L12 - HAUS6P1 region as part of a set of 3,823 independently associated variants across 2,143 genomic loci linked to tobacco and alcohol use behaviors. The study covered five phenotypes (measurable traits): smoking initiation, age at smoking onset, cigarettes per day, smoking cessation, and drinks per week. A multi-ancestry meta-regression approach was used, and the large majority of identified variants showed consistent effect sizes across ancestry clines, though polygenic risk scores - composite scores that aggregate the effects of many variants - developed in one ancestry performed poorly when applied to others.

Reported associations

• Tobacco and alcohol use behaviors: rs1174749, in the POM121L12 - HAUS6P1 region, is among 3,823 independently associated variants from 2,143 loci identified across five tobacco and alcohol use phenotypes in a multi-ancestry GWAS of approximately 3.4 million individuals. The specific phenotype or phenotypes directly tied to this variant are not detailed in the provided study excerpt.

Evidence quality The study reporting this association used a sample of approximately 3.4 million individuals drawn from 60 cohorts, placing it among the largest GWAS of tobacco and alcohol use conducted. The multi-ancestry design, with roughly 21% non-European participants spanning African, East Asian, and admixed American ancestry groups, improves both locus discovery and fine-mapping (the process of narrowing down which specific variant in a region is likely responsible for an association). A significance threshold of P < 5 x 10^-9 was applied, and only 17 of 3,823 sentinel variants (0.7%) had posterior probabilities of replication below 0.99 and were excluded from final reporting. The provided study text does not include variant-specific effect sizes or the precise phenotype(s) associated with rs1174749, which limits detailed evaluation of this specific locus. Evidence should be considered preliminary for this variant until variant-level summary statistics are reviewed directly.

Lifestyle considerations No lifestyle considerations on file for this variant.