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Genetics of 35 blood and urine biomarkers in the UK Biobank
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Genetics of 35 blood and urine biomarkers in the UK Biobank
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Journal Article
Genetics of 35 blood and urine biomarkers in the UK Biobank
2021
Overview
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.
Genetic analysis of 35 blood and urine laboratory measurements from 363,228 individuals identifies 1,857 loci associated with at least one laboratory value.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ 45/43
/ Animal Genetics and Genomics
/ Antigens
/ Biobanks
/ Biomedical and Life Sciences
/ Blood
/ Cardiovascular Diseases - genetics
/ Cardiovascular Diseases - metabolism
/ Diabetes mellitus (non-insulin dependent)
/ Diabetes Mellitus, Type 2 - genetics
/ Diabetes Mellitus, Type 2 - metabolism
/ Genetics
/ Gout
/ Histocompatibility antigen HLA
/ Humans
/ Identification and classification
/ Liver-Specific Organic Anion Transporter 1 - genetics
/ Mendelian Randomization Analysis
/ Polymorphism, Single Nucleotide
/ Proteins
/ Renal Insufficiency, Chronic
/ Risk
/ Serine Endopeptidases - genetics
/ Urine
