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Genome-Wide Association of Kidney Traits in Hispanics/Latinos Using Dense Imputed Whole-Genome Sequencing Data: The Hispanic Community Health Study/Study of Latinos.

TitleGenome-Wide Association of Kidney Traits in Hispanics/Latinos Using Dense Imputed Whole-Genome Sequencing Data: The Hispanic Community Health Study/Study of Latinos.
Publication TypePublication
Year2020
AuthorsQian H, Kowalski MH, Kramer HJ, Tao R, Lash JP, Stilp AM, Cai J, Li Y, Franceschini N
JournalCirc Genom Precis Med
Volume13
Issue4
Paginatione002891
Date Published2020 08
ISSN2574-8300
Abstract

BACKGROUND: Genetic factors that influence kidney traits have been understudied for low-frequency and ancestry-specific variants.METHODS: This study used imputed whole-genome sequencing from the Trans-Omics for Precision Medicine project to identify novel loci for estimated glomerular filtration rate and urine albumin-to-creatinine ratio in up to 12 207 Hispanics/Latinos. Replication was performed in the Women's Health Initiative and the UK Biobank when variants were available.RESULTS: Two low-frequency intronic variants were associated with estimated glomerular filtration rate (rs58720902 at , minor allele frequency=0.01, =1.6×10) or urine albumin-to-creatinine ratio (rs527493184 at , minor allele frequency=0.002, =1.1×10). An additional variant at (rs2422935, minor allele frequency=0.54, =2.89×10) was significantly associated with estimated glomerular filtration rate in meta-analysis with replication samples. We also identified 2 known loci for urine albumin-to-creatinine ratio ( rs116907128, =5.6×10 and rs344, =9.3×10) and validated 8 loci for urine albumin-to-creatinine ratio previously identified in the UK Biobank.CONCLUSIONS: Our study shows gains in gene discovery when using dense imputation from multi-ethnic whole-genome sequencing data in admixed Hispanics/Latinos. It also highlights limitations in genetic research of kidney traits, including the lack of suitable replication samples for variants that are more common in non-European ancestry and those at low frequency in populations.

DOI10.1161/CIRCGEN.119.002891
Alternate JournalCirc Genom Precis Med
PubMed ID32600054
PubMed Central IDPMC7442703
Grant ListHHSN268201300005C / HL / NHLBI NIH HHS / United States
P30 ES010126 / ES / NIEHS NIH HHS / United States
R01 HL120393 / HL / NHLBI NIH HHS / United States
R21 HL140385 / HL / NHLBI NIH HHS / United States
R01 DK117445 / DK / NIDDK NIH HHS / United States
N01HC65236 / HL / NHLBI NIH HHS / United States
N01HC65235 / HL / NHLBI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
N01HC65234 / HL / NHLBI NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
HHSN268201800001C / HL / NHLBI NIH HHS / United States
N01HC65237 / HL / NHLBI NIH HHS / United States
R21 HL123677 / HL / NHLBI NIH HHS / United States
R01 MD012765 / MD / NIMHD NIH HHS / United States
R01 HL117626 / HL / NHLBI NIH HHS / United States
UL1 TR001881 / TR / NCATS NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
N01HC65233 / HL / NHLBI NIH HHS / United States
MS#: 
0931
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