Genetics of skeletal proportions across two different populations.

Bartell E., Lin K., Tsuo K., Gan W., Vedantam S., Cole JB., Baronas JM., Yengo L., Marouli E., Amariuta T., Chen Z., Li L., GIANT consortium ., China Kadoorie Biobank Collaborative Group ., Renthal NE., Jacobsen CM., Salem RM., Walters RG., Hirschhorn JN.

Human height can be divided into sitting height and leg length. These measures reflect the growth of different parts of the skeleton whose relative proportions are captured by the ratio of sitting to total height (the sitting height ratio [SHR]). Height is a highly heritable trait, and its genetic basis has been well studied. However, the genetic determinants of skeletal proportion are much less well characterized. Expanding substantially on past work, we performed a genome-wide association study (GWAS) of the SHR in ∼450,000 individuals with European ancestry and ∼100,000 individuals with East Asian ancestry from the UK and China Kadoorie Biobanks, respectively. We identified 565 loci independently associated with the SHR, including all genomic regions implicated in prior GWASs in these ancestries. While SHR loci significantly overlap height-associated loci (p < 0.001), the fine-mapped SHR signals are often distinct from height signals. We also used fine-mapped signals to identify 36 credible sets with heterogeneous effects across ancestries. Lastly, we used the SHR, sitting height, and leg length to identify genetic variation acting on specific body regions rather than on overall human height.

DOI

10.1016/j.ajhg.2026.02.015

Type

Journal article

Publication Date

2026-04-02T00:00:00+00:00

Volume

113

Pages

794 - 808

Total pages

14

Keywords

GWAS, body proportion, fine-mapping, gene prioritization, gene set enrichment analysis, genome-wide association study, growth, height, sitting height ratio, trans-ancestry, Humans, Genome-Wide Association Study, Body Height, Asian People, Male, China, Female, Polymorphism, Single Nucleotide, White People, United Kingdom, Quantitative Trait Loci, Bone and Bones, Genetics, Population

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