TY - JOUR
T1 - Genome-wide polygenic score to predict chronic kidney disease across ancestries
AU - Khan, Atlas
AU - Turchin, Michael C.
AU - Patki, Amit
AU - Srinivasasainagendra, Vinodh
AU - Shang, Ning
AU - Nadukuru, Rajiv
AU - Jones, Alana C.
AU - Malolepsza, Edyta
AU - Dikilitas, Ozan
AU - Kullo, Iftikhar J.
AU - Schaid, Daniel J.
AU - Karlson, Elizabeth
AU - Ge, Tian
AU - Meigs, James B.
AU - Smoller, Jordan W.
AU - Lange, Christoph
AU - Crosslin, David R.
AU - Jarvik, Gail P.
AU - Bhatraju, Pavan K.
AU - Hellwege, Jacklyn N.
AU - Chandler, Paulette
AU - Torvik, Laura Rasmussen
AU - Fedotov, Alex
AU - Liu, Cong
AU - Kachulis, Christopher
AU - Lennon, Niall
AU - Abul-Husn, Noura S.
AU - Cho, Judy H.
AU - Ionita-Laza, Iuliana
AU - Gharavi, Ali G.
AU - Chung, Wendy K.
AU - Hripcsak, George
AU - Weng, Chunhua
AU - Nadkarni, Girish
AU - Irvin, Marguerite R.
AU - Tiwari, Hemant K.
AU - Kenny, Eimear E.
AU - Limdi, Nita A.
AU - Kiryluk, Krzysztof
N1 - Funding Information:
This work was funded by the National Human Genome Research Institute eMERGE-IV grant nos. 2U01HG008680-05, 1U01HG011167-01 and 1U01HG011176-01. Additional sources of funding included grant nos. UG3DK114926 (K.K.), RC2DK116690 (K.K.), R01LM013061 (C.W., K.K.), K25DK128563 (A.K.), UL1TR001873 (A.K., K.K.), R01HL151855 (J.B.M.) and UM1DK078616 (J.B.M.). The parent REGARDS study was supported by cooperative agreement no. U01NS041588 cofunded by the National Institute of Neurological Disorders and Stroke and the National Institute on Aging, the National Institutes of Health (NIH) and the Department of Health and Human Services. The HyperGEN (R01HL055673), GenHAT (R01HL123782) and WPC (R01HL092173, K24HL133373) studies were all supported by the NHLBI. Parts of this study were conducted using the UKBB resource under UKBB project no. 41849. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Funding Information:
This work was funded by the National Human Genome Research Institute eMERGE-IV grant nos. 2U01HG008680-05, 1U01HG011167-01 and 1U01HG011176-01. Additional sources of funding included grant nos. UG3DK114926 (K.K.), RC2DK116690 (K.K.), R01LM013061 (C.W., K.K.), K25DK128563 (A.K.), UL1TR001873 (A.K., K.K.), R01HL151855 (J.B.M.) and UM1DK078616 (J.B.M.). The parent REGARDS study was supported by cooperative agreement no. U01NS041588 cofunded by the National Institute of Neurological Disorders and Stroke and the National Institute on Aging, the National Institutes of Health (NIH) and the Department of Health and Human Services. The HyperGEN (R01HL055673), GenHAT (R01HL123782) and WPC (R01HL092173, K24HL133373) studies were all supported by the NHLBI. Parts of this study were conducted using the UKBB resource under UKBB project no. 41849. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2022/7
Y1 - 2022/7
N2 - 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.
AB - 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.
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U2 - 10.1038/s41591-022-01869-1
DO - 10.1038/s41591-022-01869-1
M3 - Article
C2 - 35710995
AN - SCOPUS:85132432687
SN - 1078-8956
VL - 28
SP - 1412
EP - 1420
JO - Nature Medicine
JF - Nature Medicine
IS - 7
ER -