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Genetics of 35 blood and urine biomarkers in the UK Biobank

2021; Nature Portfolio; Volume: 53; Issue: 2 Linguagem: Inglês

10.1038/s41588-020-00757-z

1546-1718

Nasa Sinnott-Armstrong, Yosuke Tanigawa, David Amar, Nina Mars, Christian Benner, Matthew Aguirre, Guhan Venkataraman, Michael Wainberg, Hanna M. Ollila, Tuomo Kiiskinen, Aki S. Havulinna, James P. Pirruccello, Junyang Qian, Anna Shcherbina, Fátima Rodríguez, Themistocles L. Assimes, Vineeta Agarwala, Robert Tibshirani, Trevor Hastie, Samuli Ripatti, Jonathan K. Pritchard, Mark J. Daly, Manuel A. Rivas,

Liver Disease Diagnosis and Treatment

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 1,857 loci associated with at least one trait, 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. Genetic analysis of 35 blood and urine laboratory measurements from 363,228 individuals identifies 1,857 loci associated with at least one laboratory value.