期刊
NATURE GENETICS
卷 53, 期 2, 页码 185-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41588-020-00757-z
关键词
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资金
- Common Fund of the Office of the Director of the National Institutes of Health (NIH)
- NCI
- National Human Genome Research Institute (NHGRI)
- NHLBI
- NIDA
- NIMH
- NINDS
- NHGRI of the NIH [R01HG010140, R01EB001988-21, R01HG008140]
- Department of Defense through a National Defense Science and Engineering grant
- Stanford Graduate Fellowship
- Funai Overseas Scholarship from the Funai Foundation for Information Technology
- Stanford University School of Medicine
- Academy of Finland [331671, 309643]
- National Heart, Lung, and Blood Institute [1K01HL144607]
- Business Finland [HUS 4685/31/2016, UH 4386/31/2016]
- AbbVie Inc
- AstraZeneca UK Ltd.
- Biogen MA Inc.
- Celgene Corporation
- Celgene International II Sarl
- Genentech Inc
- Merck Sharp Dohme Corp
- Pfizer Inc.
- GlaxoSmithKline Intellectual Property Development Ltd.
- Sanofi US Services Inc.
- Maze Therapeutics Inc.
- Janssen Biotech Inc.
- Novartis AG
- NIH Center for Multi-and Trans-ethnic Mapping of Mendelian and Complex Diseases grant [5U01 HG009080]
- Stanford University
- Stanford Research Computing Center
- Academy of Finland (AKA) [309643, 331671, 309643, 331671] Funding Source: Academy of Finland (AKA)
The study evaluated the genetic basis of 35 blood and urine laboratory measurements in the UK Biobank, identifying 1,857 loci associated with at least one trait. Through Mendelian randomization analysis, 51 causal relationships were discovered, including previously known agonistic effects of urate on gout and cystatin C on stroke. Finally, by developing polygenic risk scores and building 'multi-PRS' models, genetic risk stratification for common diseases was improved.
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.
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