Genetics of skeletal proportions in two different populations.
Genetics of skeletal proportions in two different populations.
复制标题
两个不同人群骨骼比例的遗传学。
DOI：
10.1101/2023.05.22.541772
复制
发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Renthal,No
中科院分区：
文献类型：
--
作者：
Bartell,Eric;Lin,Kuang;Tsuo,Kristin;Gan,Wei;Vedantam,Sailaja;Cole,JoanneB;Baronas,JohnM;Yengo,Loic;Marouli,Eirini;Amariuta,Tiffany;Chen,Zhengming;Li,Liming;GIANTconsortium;ChinaKadoorieBiobankCollaborativeGroup;Renthal,No
人体身高可分为坐高和腿长，反映了骨骼不同部位的生长情况，各部位的相对比例用坐高与总高的比值（坐高比，SHR）来表示。身高是一种高度遗传的特征，其遗传基础已得到充分研究。然而，骨骼比例的遗传决定因素尚不清楚。我们在过去工作的基础上进行了实质性扩展，对来自英国和中国嘉道理生物库的约 450,000 名欧洲血统个体和约 100,000 名东亚血统个体进行了 SHR 全基因组关联研究 (GWAS)。我们鉴定了 565 个与 SHR 独立相关的基因座，包括这些祖先中先前 GWAS 涉及的所有基因组区域。虽然 SHR 位点很大程度上与高度相关位点重叠 (P < 0.001)，但精细映射的 SHR 信号通常与高度不同。我们还使用精细映射的信号来识别 36 个可信的集合，这些集合在不同的祖先中具有异质效应。最后，我们使用 SHR、坐高和腿长来识别作用于特定身体区域而不是人类整体身高的遗传变异。
Human height can be divided into sitting height and leg length, reflecting growth of different parts of the skeleton whose relative proportions are captured by the ratio of sitting to total height (as 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 SHR in ∼450,000 individuals with European ancestry and ∼100,000 individuals with East Asian ancestry from the UK and China Kadoorie Biobanks. We identified 565 loci independently associated with SHR, including all genomic regions implicated in prior GWAS in these ancestries. While SHR loci largely overlap height-associated loci (P < 0.001), the fine-mapped SHR signals were often distinct from height. We additionally used fine-mapped signals to identify 36 credible sets with heterogeneous effects across ancestries. Lastly, we used SHR, sitting height, and leg length to identify genetic variation acting on specific body regions rather than on overall human height.