Genetics of 35 blood and urine biomarkers in the UK Biobank View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2021-01-18

AUTHORS

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

ABSTRACT

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. More... »

PAGES

185-194

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  • Journal

    TITLE

    Nature Genetics

    ISSUE

    2

    VOLUME

    53

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41588-020-00757-z

    DOI

    http://dx.doi.org/10.1038/s41588-020-00757-z

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1134661761

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/33462484


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