GWAS of three molecular traits highlights core genes and pathways alongside a highly polygenic background

Author:

Sinnott-Armstrong Nasa1ORCID,Naqvi Sahin12ORCID,Rivas Manuel3,Pritchard Jonathan K14ORCID

Affiliation:

1. Department of Genetics, Stanford University, Stanford, United States

2. Department of Chemical and Systems Biology, Stanford University, Stanford, United States

3. Department of Biomedical Data Sciences, Stanford University, Stanford, United States

4. Department of Biology, Stanford University, Stanford, United States

Abstract

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 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.

Funder

American Society for Engineering Education

Stanford University

National Human Genome Research Institute

Helen Hay Whitney Foundation

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

Reference126 articles.

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