rs10745432 (MGAT4C): Tobacco and Alcohol Use Variant

Key takeaways

• rs10745432 sits in or near the MGAT4C gene, which encodes a glycan-processing enzyme.
• This variant is catalogued in one of the largest multi-ancestry GWAS of tobacco and alcohol use, covering 3.4 million people from 60 cohorts.
• The study included African, American admixed, East Asian, and European ancestry groups, and found most variant effects were consistent across them.
• Specific effect-size data for rs10745432 are not detailed in the available study excerpt.
• Polygenic risk scores for tobacco and alcohol use built from one ancestry group transferred poorly to others.

What the research says A multi-ancestry genome-wide association study (GWAS) meta-analysis of tobacco and alcohol use behaviors encompassed approximately 3.4 million individuals across 60 cohorts and identified 3,823 independently associated variants across 2,143 genomic loci. Studied phenotypes included smoking initiation (n = 3,383,199), age of smoking onset (n = 728,826), cigarettes per day (n = 784,353), smoking cessation (n = 1,400,535), and drinks per week (n = 2,965,643). Increasing sample size and genetic diversity improved both locus identification and fine-mapping resolution, while the majority of associated variants showed consistent effect sizes across ancestry groups.

Reported associations

• Tobacco use behaviors: The study examined smoking initiation, age of smoking onset, cigarettes per day, and smoking cessation across samples ranging from 728,826 to 3,383,199 individuals; rs10745432 at this locus falls within the research scope, though variant-level statistics are not available in the provided excerpt.
• Alcohol use: Drinks per week was also a studied phenotype (n = 2,965,643); whether rs10745432 is specifically associated with this trait is not stated in the provided text.

Evidence quality The parent study applied a discovery threshold of p < 5 x 10-9 and used a cross-validation approach to estimate replication probability, with only 0.7% of sentinel variants falling below a posterior replication probability of 0.99. The overall sample of approximately 3.4 million individuals across diverse ancestry groups represents one of the largest GWAS efforts in behavioral genetics to date. However, the available study excerpt does not include variant-level summary statistics, odds ratios, or beta coefficients specifically for rs10745432. Independent replication for this specific variant is not documented in the provided text, and the evidence base for specific claims about rs10745432 must be considered incomplete pending access to the full supplementary data.

Lifestyle considerations No lifestyle considerations on file for this variant.