| Literature DB >> 35710995 |
Atlas Khan1, Michael C Turchin2, Amit Patki3, Vinodh Srinivasasainagendra3, Ning Shang1, Rajiv Nadukuru4, Alana C Jones5, Edyta Malolepsza6, Ozan Dikilitas7, Iftikhar J Kullo7, Daniel J Schaid7, Elizabeth Karlson8, Tian Ge9, James B Meigs10,11,12, Jordan W Smoller9, Christoph Lange13, David R Crosslin14, Gail P Jarvik15, Pavan K Bhatraju16, Jacklyn N Hellwege17, Paulette Chandler18, Laura Rasmussen Torvik19, Alex Fedotov20, Cong Liu21, Christopher Kachulis6, Niall Lennon6, Noura S Abul-Husn2,22,23, Judy H Cho4, Iuliana Ionita-Laza24, Ali G Gharavi1, Wendy K Chung25, George Hripcsak21, Chunhua Weng21, Girish Nadkarni4, Marguerite R Irvin5, Hemant K Tiwari3, Eimear E Kenny2,22,26, Nita A Limdi27, Krzysztof Kiryluk28.
Abstract
Chronic kidney disease (CKD) is a common complex condition associated with high morbidity and mortality. Polygenic prediction could enhance CKD screening and prevention; however, this approach has not been optimized for ancestrally diverse populations. By combining APOL1 risk genotypes with genome-wide association studies (GWAS) of kidney function, we designed, optimized and validated a genome-wide polygenic score (GPS) for CKD. The new GPS was tested in 15 independent cohorts, including 3 cohorts of European ancestry (n = 97,050), 6 cohorts of African ancestry (n = 14,544), 4 cohorts of Asian ancestry (n = 8,625) and 2 admixed Latinx cohorts (n = 3,625). We demonstrated score transferability with reproducible performance across all tested cohorts. The top 2% of the GPS was associated with nearly threefold increased risk of CKD across ancestries. In African ancestry cohorts, the APOL1 risk genotype and polygenic component of the GPS had additive effects on the risk of CKD.Entities:
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Year: 2022 PMID： 35710995 PMCID： PMC9329233 DOI： 10.1038/s41591-022-01869-1
Source DB: PubMed Journal: Nat Med ISSN： 1078-8956 Impact factor: 87.241