|Title||Genome-Wide Association of Kidney Traits in Hispanics/Latinos Using Dense Imputed Whole-Genome Sequencing Data: The Hispanic Community Health Study/Study of Latinos.|
|Publication Type||Journal Article|
|Year of Publication||2020|
|Authors||Qian H, Kowalski MH, Kramer HJ, Tao R, Lash JP, Stilp AM, Cai J, Li Y|
|Secondary Authors||Franceschini N|
|Journal||Circ Genom Precis Med|
|Date Published||2020 Aug|
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.
|Alternate Journal||Circ Genom Precis Med|
|PubMed Central ID||PMC7442703|
|Grant List||HHSN268201300005C / HL / NHLBI 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
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
P30 DK063491 / DK / NIDDK NIH HHS / United States
N01HC65233 / HL / NHLBI NIH HHS / United States