Genetics of Chronic Kidney Disease Stages Across Ancestries: The PAGE Study. Lin, B. M., Nadkarni, G. N., Tao, R., Graff, M., Fornage, M., Buyske, S., Matise, T. C., Highland, H. M., Wilkens, L. R., Carlson, C. S., Park, S. L., Setiawan, V. W., Ambite, J. L., Heiss, G., Boerwinkle, E., Lin, D., Morris, A. P., Loos, R. J. F., Kooperberg, C., North, K. E., Wassel, C. L., & Franceschini, N. Frontiers in genetics, 10:494, 2019. ![Genetics of Chronic Kidney Disease Stages Across Ancestries: The PAGE Study. [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex Chronic kidney disease (CKD) is common and disproportionally burdens United States ethnic minorities. Its genetic determinants may differ by disease severity and clinical stages. To uncover genetic factors associated CKD severity among high-risk ethnic groups, we performed genome-wide association studies (GWAS) in diverse populations within the Population Architecture using Genomics and Epidemiology (PAGE) study. We assembled multi-ethnic genome-wide imputed data on CKD non-overlapping cases [4,150 mild to moderate CKD, 1,105 end-stage kidney disease (ESKD)] and non-CKD controls for up to 41,041 PAGE participants (African Americans, Hispanics/Latinos, East Asian, Native Hawaiian, and American Indians). We implemented a generalized estimating equation approach for GWAS using ancestry combined data while adjusting for age, sex, principal components, study, and ethnicity. The GWAS identified a novel genome-wide associated locus for mild to moderate CKD nearby (rs10906850, = 3.7 × 10 ) that replicated in the United Kingdom Biobank white British ( = 0.008). Several variants at the locus were associated with ESKD including the G1 rs73885319 ( = 1.2 × 10 ). There was no overlap among associated loci for CKD and ESKD traits, even at the previously reported locus ( = 0.76 for CKD). Several additional loci were associated with CKD or ESKD at -values below the genome-wide threshold. These loci were often driven by variants more common in non-European ancestry. Our genetic study identified a novel association at for CKD and showed for the first time strong associations of the variants with ESKD across multi-ethnic populations. Our findings suggest differences in genetic effects across CKD severity and provide information for study design of genetic studies of CKD in diverse populations.
@article{LinNadkarniTaoEtAl2019,
abstract = {Chronic kidney disease (CKD) is common and disproportionally burdens United States ethnic minorities. Its genetic determinants may differ by disease severity and clinical stages. To uncover genetic factors associated CKD severity among high-risk ethnic groups, we performed genome-wide association studies ({GWAS}) in diverse populations within the {Population Architecture using Genomics and Epidemiology} (PAGE) study. We assembled multi-ethnic genome-wide imputed data on CKD non-overlapping cases [4,150 mild to moderate CKD, 1,105 end-stage kidney disease (ESKD)] and non-CKD controls for up to 41,041 PAGE participants (African Americans, Hispanics/Latinos, East Asian, Native Hawaiian, and American Indians). We implemented a generalized estimating equation approach for {GWAS} using ancestry combined data while adjusting for age, sex, principal components, study, and ethnicity. The {GWAS} identified a novel genome-wide associated locus for mild to moderate CKD nearby (rs10906850, = 3.7 × 10 ) that replicated in the United Kingdom Biobank white British ( = 0.008). Several variants at the locus were associated with ESKD including the G1 rs73885319 ( = 1.2 × 10 ). There was no overlap among associated loci for CKD and ESKD traits, even at the previously reported locus ( = 0.76 for CKD). Several additional loci were associated with CKD or ESKD at -values below the genome-wide threshold. These loci were often driven by variants more common in non-European ancestry. Our genetic study identified a novel association at for CKD and showed for the first time strong associations of the variants with ESKD across multi-ethnic populations. Our findings suggest differences in genetic effects across CKD severity and provide information for study design of genetic studies of CKD in diverse populations.},
author = {Lin, Bridget M. and Nadkarni, Girish N. and Tao, Ran and Graff, Mariaelisa and Fornage, Myriam and Buyske, Steven and Matise, Tara C. and Highland, Heather M. and Wilkens, Lynne R. and Carlson, Christopher S. and Park, S. Lani and Setiawan, V. Wendy and Ambite, Jose Luis and Heiss, Gerardo and Boerwinkle, Eric and Lin, Dan-Yu and Morris, Andrew P. and Loos, Ruth J. F. and Kooperberg, Charles and North, Kari E. and Wassel, Christina L. and Franceschini, Nora},
country = {Switzerland},
doi = {10.3389/fgene.2019.00494},
issn = {1664-8021},
issn-linking = {1664-8021},
journal = {Frontiers in genetics},
keywords = {APOL1; chronic kidney disease stages; diverse populations; end stage kidney disease; genetics; genome-wide association studies; single nucleotide polymorphisms},
nlm-id = {101560621},
owner = {NLM},
pages = {494},
pmc = {PMC6544117},
pmid = {31178898},
url = {https://pubmed.ncbi.nlm.nih.gov/31178898/},
pubmodel = {Electronic-eCollection},
pubstate = {epublish},
revised = {2020-09-28},
title = {Genetics of Chronic Kidney Disease Stages Across Ancestries: The {PAGE} Study.},
volume = {10},
year = {2019},
bdsk-url-1 = {https://pubmed.ncbi.nlm.nih.gov/31178898/},
bdsk-url-2 = {https://doi.org/10.3389/fgene.2019.00494}}
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To uncover genetic factors associated CKD severity among high-risk ethnic groups, we performed genome-wide association studies (GWAS) in diverse populations within the Population Architecture using Genomics and Epidemiology (PAGE) study. We assembled multi-ethnic genome-wide imputed data on CKD non-overlapping cases [4,150 mild to moderate CKD, 1,105 end-stage kidney disease (ESKD)] and non-CKD controls for up to 41,041 PAGE participants (African Americans, Hispanics/Latinos, East Asian, Native Hawaiian, and American Indians). We implemented a generalized estimating equation approach for GWAS using ancestry combined data while adjusting for age, sex, principal components, study, and ethnicity. The GWAS identified a novel genome-wide associated locus for mild to moderate CKD nearby (rs10906850, = 3.7 × 10 ) that replicated in the United Kingdom Biobank white British ( = 0.008). Several variants at the locus were associated with ESKD including the G1 rs73885319 ( = 1.2 × 10 ). 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