Genetics of 35 blood and urine biomarkers in the UK Biobank
Top Cited Papers
- 18 January 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Genetics
- Vol. 53 (2), 185-194
- https://doi.org/10.1038/s41588-020-00757-z
Abstract
Clinical laboratory tests are a critical component of the continuum of care. We evaluate the genetic basis of 35 blood and urine laboratory measurements in the UK Biobank (n = 363,228 individuals). We identify 5,794 independent loci associated with at least one trait (p < 5 × 10−9), containing 3,374 fine-mapped associations and additional sets of large-effect (>0.1 s.d.) protein-altering, human leukocyte antigen (HLA) and copy number variant (CNV) associations. Through Mendelian randomization (MR) analysis, we discover 51 causal relationships, including previously known agonistic effects of urate on gout and cystatin C on stroke. Finally, we develop polygenic risk scores (PRSs) for each biomarker and build ‘multi-PRS’ models for diseases using 35 PRSs simultaneously, which improved chronic kidney disease, type 2 diabetes, gout and alcoholic cirrhosis genetic risk stratification in an independent dataset (FinnGen; n = 135,500) relative to single-disease PRSs. Together, our results delineate the genetic basis of biomarkers and their causal influences on diseases and improve genetic risk stratification for common diseases.Keywords
Funding Information
- U.S. Department of Health & Human Services | National Institutes of Health (1K01HL144607, R01EB001988-21, R01HG008140, R01HG010140, 5U01 HG009080)
- The Department of Defense through a National Defense Science and Engineering Grant and by a Stanford Graduate Fellowship
- Funai Overseas Scholarship from the Funai Foundation for Information Technology and the Stanford University School of Medicine
- Academy of Finland (#331671, #309643)
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