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Genome-Wide Admixture Mapping of Estimated Glomerular Filtration Rate and Chronic Kidney Disease Identifies European and African Ancestry-of-Origin Loci in Hispanic and Latino Individuals in the United States.

TitleGenome-Wide Admixture Mapping of Estimated Glomerular Filtration Rate and Chronic Kidney Disease Identifies European and African Ancestry-of-Origin Loci in Hispanic and Latino Individuals in the United States.
Publication TypePublication
Year2022
AuthorsHorimoto ARVR, Xue D, Cai J, Lash JP, Daviglus ML, Franceschini N, Thornton TA
JournalJ Am Soc Nephrol
Volume33
Issue1
Pagination77-87
Date Published2022 01
ISSN1533-3450
KeywordsAdult, African Americans, Chromosome Mapping, Female, Genetic Loci, genome-wide association study, Glomerular Filtration Rate, Hispanic or Latino, Humans, Male, Middle Aged, Renal Insufficiency, Chronic, United States, Whites
Abstract

BACKGROUND: Admixture mapping is a powerful approach for gene mapping of complex traits that leverages the diverse genetic ancestry in populations with recent admixture, such as Hispanic or Latino individuals in the United States. These individuals have an increased risk of CKD.METHODS: We performed genome-wide admixture mapping for both CKD and eGFR in a sample of 12,601 participants from the Hispanic Community Health Study/Study of Latinos, with validation in a sample of 8191 Black participants from the Women's Health Initiative (WHI). We also compared the findings with those from a conventional genome-wide association study.RESULTS: Three novel ancestry-of-origin loci were identified on chromosomes 2, 14, and 15 for CKD and eGFR. The chromosome 2 locus comprises two European ancestry regions encompassing the and genes, with European ancestry at this locus associated with increased CKD risk. The chromosome 14 locus, found within the imprinted domain, was associated with lower eGFR and driven by European ancestry. The eGFR-associated locus on chromosome 15 included intronic variants of and was within an African-specific genomic region associated with higher eGFR. The genome-wide association study failed to identify significant associations in these regions. We validated the chromosome 14 and 15 loci associated with eGFR in the WHI Black participants.CONCLUSIONS: This study provides evidence of shared ancestry-specific genomic regions influencing eGFR in Hispanic or Latino individuals and Black individuals and illustrates the potential for leveraging genetic ancestry in recently admixed populations for the discovery of novel candidate loci for kidney phenotypes.

DOI10.1681/ASN.2021050617
Alternate JournalJ Am Soc Nephrol
PubMed ID34670813
PubMed Central IDPMC8763178
Grant ListUL1 TR000124 / TR / NCATS NIH HHS / United States
R01 DK117445 / DK / NIDDK NIH HHS / United States
N01 HC065237 / HC / NHLBI NIH HHS / United States
T32 AG052354 / AG / NIA NIH HHS / United States
N01 HC065233 / HC / NHLBI NIH HHS / United States
R01 MD012765 / MD / NIMHD NIH HHS / United States
N01 HC065235 / HC / NHLBI NIH HHS / United States
HHSN268201300005C / HL / NHLBI NIH HHS / United States
N01 HC065234 / HC / NHLBI NIH HHS / United States
N01 HC065236 / HC / NHLBI NIH HHS / United States
R21 HL123677 / HL / NHLBI NIH HHS / United States
MS#: 
0920
Manuscript Lead/Corresponding Author Affiliation: 
Coordinating Center - Collaborative Studies Coordinating Center - UNC at Chapel Hill
ECI: 
Yes
Manuscript Affiliation: 
Coordinating Center - Collaborative Studies Coordinating Center - UNC at Chapel Hill
Manuscript Status: 
Published