Genetics of 35 blood and urine biomarkers in the UK Biobank
Abstrak
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 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.
Topik & Kata Kunci
Penulis (20)
Nicholas A. Sinnott-Armstrong
Yosuke Tanigawa
D. Amar
N. Mars
Matthew Aguirre
G. Venkataraman
Michael Wainberg
H. Ollila
J. Pirruccello
Junyang Qian
A. Shcherbina
F. Rodriguez
T. Assimes
Vineeta Agarwala
R. Tibshirani
T. Hastie
S. Ripatti
J. Pritchard
M. Daly
M. Rivas
Akses Cepat
- Tahun Terbit
- 2020
- Bahasa
- en
- Total Sitasi
- 634×
- Sumber Database
- Semantic Scholar
- DOI
- 10.1038/s41588-020-00757-z
- Akses
- Open Access ✓