Genetics of 35 blood and urine biomarkers in the UK Biobank.

TitleGenetics of 35 blood and urine biomarkers in the UK Biobank.
Publication TypeJournal Article
Year of Publication2021
AuthorsSinnott-Armstrong, N, Tanigawa, Y, Amar, D, Mars, N, Benner, C, Aguirre, M, Venkataraman, GRam, Wainberg, M, Ollila, HM, Kiiskinen, T, Havulinna, AS, Pirruccello, JP, Qian, J, Shcherbina, A, Rodriguez, F, Assimes, TL, Agarwala, V, Tibshirani, R, Hastie, T, Ripatti, S, Pritchard, JK, Daly, MJ, Rivas, MA
Corporate AuthorsFinnGen
JournalNat Genet
Date Published2021 02
KeywordsBiological Specimen Banks, Biomarkers, Cardiovascular Diseases, Diabetes Mellitus, Type 2, DNA Copy Number Variations, Genetic Pleiotropy, HLA Antigens, Humans, Linkage Disequilibrium, Liver-Specific Organic Anion Transporter 1, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide, Proteins, Renal Insufficiency, Chronic, Serine Endopeptidases, United Kingdom

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.

Alternate JournalNat Genet
PubMed ID33462484
PubMed Central IDPMC7867639
Grant ListP30 AG059307 / AG / NIA NIH HHS / United States
R01 HG008140 / HG / NHGRI NIH HHS / United States
U01 HG009080 / HG / NHGRI NIH HHS / United States
R01 GM134483 / GM / NIGMS NIH HHS / United States
R01 EB001988 / EB / NIBIB NIH HHS / United States
T15 LM007033 / LM / NLM NIH HHS / United States
R01 HG010140 / HG / NHGRI NIH HHS / United States
K01 HL144607 / HL / NHLBI NIH HHS / United States