Apr 22, 2020

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

BioRxiv : the Preprint Server for Biology
N. Sinnott-ArmstrongJonathan K Pritchard


Genome-wide association studies (GWAS) have been used to study the genetic basis of a wide variety of complex diseases and other traits. However, for most traits it remains difficult to interpret what genes and biological processes are impacted by the top hits. Here, as a contrast, we describe UK Biobank GWAS results for three molecular traits--urate, IGF-1, and testosterone--that are biologically simpler than most diseases, and for which we know a great deal in advance about the core genes and pathways. Unlike most GWAS of complex traits, for all three traits we find that most top hits are readily interpretable. We observe huge enrichment of significant signals near genes involved in the relevant biosynthesis, transport, or signaling pathways. We show how GWAS data illuminate the biology of variation in each trait, including insights into differences in testosterone regulation between females and males. Meanwhile, in other respects the results are reminiscent of GWAS for more-complex traits. In particular, even these molecular traits are highly polygenic, with most of the variance coming not from core genes, but from thousands to tens of thousands of variants spread across most of the genome. Given that diseases are often impa...Continue Reading

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Mentioned in this Paper

Laboratory Procedures
Sequence Determinations, RNA
Embryonic Development
Gene Expression
Germ Cell Development
Morula (Embryonic Structure)

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