rs12442633 (THSD4): Common Variant Linked to Height

Key takeaways

• rs12442633 (THSD4 locus; thrombospondin type 1 domain-containing 4) is one of 12,111 common genetic variants significantly associated with adult height
• This variant was identified in one of the largest genetic studies ever conducted, covering 5,380,080 individuals across five major ancestry groups
• All identified height-associated variants together explain roughly 40% of height variability in people of European ancestry
• Effect sizes for height variants are broadly consistent across global ancestry groups
• Lower predictive accuracy in non-European populations reflects differences in linkage disequilibrium patterns rather than differing biology

What the research says This variant is one of 12,111 independent single-nucleotide polymorphisms (SNPs - positions in the genome where one DNA letter differs between individuals) found to be significantly associated with adult height in a genome-wide association study of 5,380,080 individuals across 281 studies. These SNPs cluster within 7,209 non-overlapping genomic segments with a mean size of approximately 90 kilobases, covering about 21% of the human genome. Collectively, they account for approximately 40% of phenotypic variance in height among individuals of European ancestry (or 45% when all variants in the HapMap 3 reference panel are included) and approximately 10-20% in populations of other ancestries.

Reported associations

• Adult height: rs12442633 is one of 12,111 independent SNPs significantly associated with standing height in a meta-analysis of 5,380,080 individuals from five major ancestry groups; the full complement of identified SNPs explains approximately 40% of variance in this trait in European-ancestry populations and approximately 10-20% in other ancestry groups

Evidence quality The source study (Yengo et al., Nature, 2022) is the largest height GWAS published to date, with 5,380,080 participants from 281 studies from the GIANT consortium and 23andMe. Ancestry composition was 75.8% predominantly European, 8.8% East Asian, 8.5% Hispanic with admixed ancestries, 5.5% predominantly African, and 1.4% predominantly South Asian. All 12,111 reported SNPs reached genome-wide significance thresholds. Specific per-variant statistics for this locus - such as its individual effect size, p-value, or associated allele - are not reported in the available study excerpt and would appear in the supplementary data of the original publication. Effect sizes and associated regions were found to be broadly consistent across ancestry groups. The authors interpret reduced predictive accuracy in non-European populations as stemming from linkage disequilibrium differences and allele frequency variation rather than differing biological effects. No conflicting findings regarding this variant are reported in the available study data.

Lifestyle considerations No lifestyle considerations on file for this variant.