Genome-wide association studies (GWAS) have been used to study the genetic basis of a wide variety of complex diseases and other traits. We describe UK Biobank GWAS results for three molecular traits-urate, IGF-1, and testosterone-with better-understood biology than most other complex traits. We find that many of the most significant hits are readily and surprisingly interpretable. We observe huge enrichment of associations near genes involved in the relevant biosynthesis, transport, or signaling pathways. We show how GWAS data illuminate the biology of each trait, including differences in testosterone regulation between females and males. At the same time, even these molecular traits are highly polygenic, with many thousands of variants spread across the genome contributing to trait variance. In summary, for these three molecular traits we identify strong enrichment of signal in putative core gene sets, even while most of the SNP-based heritability is driven by a massively polygenic background.

中文翻译：

---

具有三个分子特征的GWAS突出显示了核心基因和途径以及高度多基因的背景

全基因组关联研究（GWAS）已用于研究多种复杂疾病和其他性状的遗传基础。我们描述了英国生物库GWAS的三个分子特性-尿酸盐，IGF-1和睾丸激素-比大多数其他复杂特性更容易理解的生物学结果。我们发现许多最重要的命中词都易于理解且令人惊讶。我们观察到与相关生物合成，运输或信号传导途径有关的基因附近的缔合体大量富集。我们展示了GWAS数据如何阐明每个特征的生物学特性，包括雌雄之间睾丸激素调节的差异。同时，即使这些分子性状也是高度多基因的，成千上万的变异遍布基因组，从而导致性状变异。综上所述，