Most genome-wide association studies have been of European individuals, even though most genetic variation in humans is seen only in non-European samples. To search for novel loci associated with blood lipid levels and clarify the mechanism of action at previously identified lipid loci, we used an exome array to examine protein-coding genetic variants in 47,532 East Asian individuals. We identified 255 variants at 41 loci that reached chip-wide significance, including 3 novel loci and 14 East Asian-specific coding variant associations. After a meta-analysis including >300,000 European samples, we identified an additional nine novel loci. Sixteen genes were identified by protein-altering variants in both East Asians and Europeans, and thus are likely to be functional genes. Our data demonstrate that most of the low-frequency or rare coding variants associated with lipids are population specific, and that examining genomic data across diverse ancestries may facilitate the identification of functional genes at associated loci.

中文翻译：

---

外显子组芯片荟萃分析确定了导致脂质水平和冠状动脉疾病的新基因座和东亚特异性编码变体。

大多数全基因组关联研究都是针对欧洲个体的，尽管人类的大多数遗传变异仅在非欧洲样本中可见。为了寻找与血脂水平相关的新基因座并阐明先前确定的脂质基因座的作用机制，我们使用外显子组阵列检查了 47,532 名东亚人的蛋白质编码遗传变异。我们在 41 个基因座上鉴定了 255 个变体，这些变体达到了芯片范围内的显着性，包括 3 个新基因座和 14 个东亚特异性编码变体关联。在对超过 300,000 个欧洲样本进行荟萃分析后，我们确定了另外 9 个新基因座。在东亚人和欧洲人中，有 16 个基因被蛋白质改变变异体鉴定，因此很可能是功能基因。