TY - JOUR
T1 - Genetics of 35 blood and urine biomarkers in the UK Biobank
AU - Sinnott-Armstrong, Nasa
AU - Tanigawa, Yosuke
AU - Amar, David
AU - Mars, Nina
AU - Benner, Christian
AU - Aguirre, Matthew
AU - Venkataraman, Guhan Ram
AU - Wainberg, Michael
AU - Ollila, Hanna M.
AU - Kiiskinen, Tuomo
AU - Havulinna, Aki S.
AU - Pirruccello, James P.
AU - Qian, Junyang
AU - Shcherbina, Anna
AU - Rodriguez, Fatima
AU - Assimes, Themistocles L.
AU - Agarwala, Vineeta
AU - Tibshirani, Robert
AU - Hastie, Trevor
AU - Ripatti, Samuli
AU - Pritchard, Jonathan K.
AU - Daly, Mark J.
AU - Rivas, Manuel A.
N1 - Publisher Copyright: © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2021/2
Y1 - 2021/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85100123081&partnerID=8YFLogxK
U2 - 10.1038/s41588-020-00757-z
DO - 10.1038/s41588-020-00757-z
M3 - مقالة
C2 - 33462484
SN - 1061-4036
VL - 53
SP - 185
EP - 194
JO - Nature Genetics
JF - Nature Genetics
IS - 2
ER -
