rs12410416 (DNM3): adult height in East Asians

Key takeaways

• rs12410416, located near the DNM3 gene (Dynamin 3, a protein involved in cellular membrane dynamics), is associated with adult height in East Asian populations.
• Evidence comes from a meta-analysis of over 93,000 East Asian individuals, among the largest height GWAS focused on this ancestry group at the time of publication.
• Some variants at this genomic region are rare in Europeans (minor allele frequency below 5%), which explains why they were missed in earlier European-centered height studies.
• GTEx data links the alternative allele of this variant to reduced expression of a nearby gene (ENSG00000287336) in tibial nerve tissue.
• No lifestyle interventions have been studied in relation to this specific locus.

What the research says A meta-analysis in 93,926 East Asian individuals identified 98 loci for adult height at genome-wide significance (p < 5 x 10^-8), including 17 novel loci, collectively explaining 8.89% of height variance; seven of those novel loci had minor allele frequency below 5% in Europeans, underscoring population-specific genetic architecture PMID 25429064. A genome-wide analysis of the Taiwan Biobank identified 6,843 height-associated SNPs across 89 genomic regions in 67,452 Han Chinese participants, including 18 novel loci, with the most strongly associated regions near genes including EFEMP1, DIS3L2, ZBTB38, and GDF5 PMID 35676700. The PAGE study of 49,839 non-European participants found that diverse-ancestry cohorts reveal 27 novel loci and demonstrate effect-size heterogeneity across ancestries, highlighting that risk estimates derived in European populations do not reliably extrapolate to other groups PMID 31217584.

Reported associations

• Adult height (East Asian meta-analysis): Associated with adult stature among 17 novel loci discovered at genome-wide significance in 93,926 East Asians; all 98 identified signals together explain 8.89% of height variance PMID 25429064
• Adult height (Han Chinese cohort): Located within the broader set of 89 height-associated genomic regions identified in 67,452 Han Chinese individuals from the Taiwan Biobank, a resource that also found height positively associated with body weight, waist circumference, and hip circumference, and negatively associated with BMI, waist-hip ratio, body fat, total cholesterol, and LDL cholesterol PMID 35676700

Evidence quality The primary evidence derives from a large East Asian meta-analysis (n=93,926) achieving p < 5 x 10^-8 PMID 25429064. Supporting evidence comes from the independent Taiwan Biobank cohort (n=67,452 Han Chinese) PMID 35676700. The PAGE study (n=49,839 non-European) adds a cautionary framework: effect sizes from European GWAS show heterogeneity across ancestries and may not transfer reliably PMID 31217584. No conflicting findings are reported across these three studies. The 8.89% of height variance explained by all 98 loci in the East Asian meta-analysis remains a fraction of estimated total height heritability, indicating many contributing loci remain undiscovered. Individual per-allele effect sizes for rs12410416 specifically are not reported in the provided study texts.

Tissue-specific expression effects

• ENSG00000287336: The alternative allele of rs12410416 is associated with reduced expression of this gene in tibial nerve tissue (GTEx v11, 953 donors, FDR < 0.05) GTEx Portal. The functional connection between this nerve-tissue expression change and height-related biology is not addressed by the studies provided.

Lifestyle considerations No lifestyle considerations on file for this variant.