rs12449311 (NATD1): Height-Associated Genetic Variant

Key takeaways

• rs12449311 near the NATD1 gene is linked to adult human height, identified in one of the largest genetic studies ever conducted
• The study covered approximately 5.4 million people from five major ancestry groups across 281 research projects
• 12,111 common genetic variants were found to account for nearly all the common genetic contribution to height variation
• Height-associated variants show similar effect sizes across ancestry groups, though prediction accuracy is lower outside European-ancestry populations
• Common variants together explain about 40-45% of height variation in European-ancestry populations

What the research says A genome-wide association study (a large-scale scan of the full human genome for trait-linked variants) of approximately 5.4 million individuals from 281 studies identified 12,111 independent SNPs (single-nucleotide polymorphisms, meaning single-letter changes in the DNA sequence) significantly associated with adult height, clustered within 7,209 non-overlapping genomic segments averaging around 90 kilobases in size and covering about 21% of the human genome. In European-ancestry populations, all common variants in the HapMap 3 reference panel (a widely used catalog of common human genetic variants) account for approximately 45% of height variation, while the 12,111 significant SNPs alone account for about 40%. Effect sizes and associated genomic regions were reported as broadly consistent across ancestry groups, though prediction accuracy was lower in non-European populations.

Reported associations

• Adult height: rs12449311 near NATD1 is among 12,111 independent SNPs significantly associated with adult height in a genome-wide study of approximately 5.4 million individuals; together these variants account for nearly all of the common SNP-based heritability (the portion of height variation attributable to common genetic variants) of this trait

Evidence quality This association comes from the largest height GWAS conducted to date, with approximately 5.4 million participants from 281 studies, published in Nature (2022). The sample includes approximately 4,080,687 individuals of predominantly European ancestry (75.8%), 472,730 of East Asian ancestry (8.8%), 455,180 of Hispanic or admixed ancestry (8.5%), 293,593 of African or African American ancestry (5.5%), and 77,890 of South Asian ancestry (1.4%). No specific effect size for rs12449311 alone is reported in the available study text. Effect sizes and associated genomic regions were broadly consistent across ancestry groups; lower prediction accuracy in non-European populations is attributed to differences in linkage disequilibrium (the statistical correlation between nearby genetic variants in a population) and allele frequency (how common each variant is in a given group). The authors conclude that the common variant map for height is nearly saturated for European-ancestry populations, meaning few significant common variants of meaningful size remain to be discovered in that group, though further research is needed for other ancestries.

Lifestyle considerations No lifestyle considerations on file for this variant.