rs10768692 (LRRC4C): Tobacco and Alcohol Use Variant

Key takeaways

• rs10768692 sits near LRRC4C (leucine-rich repeat-containing 4C) and LINC02741 (a long intergenic non-coding RNA), genes flagged in a 3.4-million-person tobacco and alcohol genetics study
• The identifying study included participants from diverse ancestral backgrounds, with roughly 21% of non-European ancestry
• Most variants identified in the study showed consistent effect sizes across different ancestry groups
• Polygenic risk scores for tobacco and alcohol use behaviors work poorly when applied across different ancestry groups, limiting current genetic prediction tools

What the research says A multi-ancestry genome-wide association study (GWAS, a study design that scans the entire genome to find variants statistically linked to a trait) of 3.4 million individuals, approximately 21% of non-European ancestry, identified 2,143 genomic loci and 3,823 independently associated variants across five tobacco and alcohol use phenotypes: smoking initiation (n = 3,383,199), cigarettes per day (n = 784,353), smoking cessation (n = 1,400,535), age at smoking onset (n = 728,826), and drinks per week (n = 2,965,643). All sentinel variants met a stringent significance threshold of P < 5 x 10^-9, and 99.3% had posterior replication probabilities above 0.99. Polygenic risk scores, tools that aggregate many small genetic effects into a single estimate, performed substantially worse when developed in one ancestry group and applied to another.

Reported associations

• Tobacco and alcohol use phenotypes: rs10768692, located near LRRC4C and LINC02741 (this locus), was among the variants identified in a multi-ancestry GWAS spanning smoking initiation, cigarettes per day, smoking cessation, age at smoking onset, and drinks per week across up to 3.4 million participants; the specific phenotype or phenotypes most strongly associated with this variant are not detailed in the available study text

Evidence quality The identifying study is a large, well-powered multi-ancestry GWAS with sample sizes reaching up to 3.4 million individuals, representing strong statistical power. All sentinel variants passed a P < 5 x 10^-9 threshold and 99.3% met a posterior replication probability above 0.99. Including diverse ancestries improved both discovery power and fine-mapping resolution relative to European-only analyses. A large majority of identified variants showed consistent effect sizes across ancestry clines, suggesting broad generalizability at most loci. The specific phenotype assignment, effect size, and ancestry-level breakdown for rs10768692 individually are not reported in the available study text, so claims about this variant's precise biological role remain limited to its membership in this large set of identified loci.

Lifestyle considerations No lifestyle considerations on file for this variant.