Journal article
Whole genome sequence analyses of eGFR in 23,732 people representing multiple ancestries in the NHLBI trans-omics for precision medicine (TOPMed) consortium
EBioMedicine, Vol.63, pp.103157-103157
01/2021
DOI: 10.1016/j.ebiom.2020.103157
PMCID: PMC7804602
PMID: 33418499
Abstract
Genetic factors that influence kidney traits have been understudied for low frequency and ancestry-specific variants.
We combined whole genome sequencing (WGS) data from 23,732 participants from 10 NHLBI Trans-Omics for Precision Medicine (TOPMed) Program multi-ethnic studies to identify novel loci for estimated glomerular filtration rate (eGFR). Participants included European, African, East Asian, and Hispanic ancestries. We applied linear mixed models using a genetic relationship matrix estimated from the WGS data and adjusted for age, sex, study, and ethnicity.
When testing single variants, we identified three novel loci driven by low frequency variants more commonly observed in non-European ancestry (PRKAA2, rs180996919, minor allele frequency [MAF] 0.04%, P = 6.1 × 10−11; METTL8, rs116951054, MAF 0.09%, P = 4.5 × 10−9; and MATK, rs539182790, MAF 0.05%, P = 3.4 × 10−9). We also replicated two known loci for common variants (rs2461702, MAF=0.49, P = 1.2 × 10−9, nearest gene GATM, and rs71147340, MAF=0.34, P = 3.3 × 10−9, CDK12). Testing aggregated variants within a gene identified the MAF gene. A statistical approach based on local ancestry helped to identify replication samples for ancestry-specific variants.
This study highlights challenges in studying variants influencing kidney traits that are low frequency in populations and more common in non-European ancestry.
Details
- Title: Subtitle
- Whole genome sequence analyses of eGFR in 23,732 people representing multiple ancestries in the NHLBI trans-omics for precision medicine (TOPMed) consortium
- Creators
- Bridget M Lin - University of North Carolina at Chapel HillKelsey E Grinde - Macalester CollegeJennifer A Brody - University of WashingtonCharles E Breeze - National Cancer InstituteLaura M Raffield - University of North Carolina at Chapel HillJosyf C Mychaleckyj - University of VirginiaTimothy A Thornton - University of WashingtonJames A Perry - University of Maryland, BaltimoreLeslie J Baier - National Institutes of HealthLisa de las Fuentes - Washington University in St. LouisXiuqing Guo - The Lundquist InstituteBenjamin D Heavner - University of WashingtonRobert L Hanson - National Institutes of HealthYi-Jen Hung - Tri-Service General HospitalHuijun Qian - University of North Carolina at Chapel HillChao A Hsiung - National Taiwan UniversityShih-Jen Hwang - National Heart Lung and Blood InstituteMargaret R Irvin - University of Alabama at BirminghamDeepti Jain - University of WashingtonTanika N Kelly - Tulane UniversitySayuko Kobes - National Institutes of HealthLeslie Lange - University of Colorado Anschutz Medical CampusJames P Lash - University of Illinois ChicagoYun Li - University of North Carolina at Chapel HillXiaoming Liu - University of South FloridaXuenan Mi - Tulane UniversitySolomon K Musani - University of Mississippi Medical CenterGeorge J Papanicolaou - National Institutes of HealthAfshin Parsa - National Institutes of HealthAlex P Reiner - Fred Hutch Cancer CenterShabnam Salimi - University of Maryland, BaltimoreWayne H-H Sheu - Taichung Veterans General HospitalAlan R Shuldiner - University of Maryland, BaltimoreKent D Taylor - The Lundquist InstituteAlbert V Smith - University of MichiganJennifer A Smith - University of MichiganAdrienne Tin - University of Mississippi Medical CenterDhananjay Vaidya - Johns Hopkins MedicineRobert B Wallace - University of IowaKenichi Yamamoto - The University of OsakaSaori Sakaue - The University of TokyoKoichi Matsuda - The University of TokyoYoichiro Kamatani - The University of TokyoYukihide Momozawa - RIKEN Center for Integrative Medical SciencesLisa R Yanek - Johns Hopkins MedicineBetsi A Young - University of WashingtonWei Zhao - University of MichiganYukinori Okada - The University of OsakaGonzalo Abecasis - University of MichiganBruce M Psaty - University of WashingtonDonna K Arnett - University of KentuckyEric Boerwinkle - Baylor College of MedicineJianwen Cai - University of North Carolina at Chapel HillIda Yii-Der Chen - Harbor–UCLA Medical CenterAdolfo Correa - University of Mississippi Medical CenterL Adrienne Cupples - Boston UniversityJiang He - Tulane UniversitySharon LR Kardia - University of MichiganCharles Kooperberg - Fred Hutch Cancer CenterRasika A Mathias - Johns Hopkins MedicineBraxton D Mitchell - University of Maryland, BaltimoreDeborah A Nickerson - University of WashingtonSteve T Turner - Mayo ClinicRamachandran S Vasan - Boston UniversityJerome I Rotter - The Lundquist InstituteDaniel Levy - National Heart Lung and Blood InstituteHolly J Kramer - Loyola University ChicagoAnna Köttgen - Johns Hopkins UniversityStephen S Rich - University of VirginiaDan-Yu Lin - Department of Biostatistics, University of North Carolina, Chapel Hill, NC, United StatesSharon R Browning - University of WashingtonNora Franceschini - University of North Carolina at Chapel HillNHLBI Trans-Omics for Precision Medicine (TOPMed) ConsortiumTOPMed Kidney Working Group
- Resource Type
- Journal article
- Publication Details
- EBioMedicine, Vol.63, pp.103157-103157
- DOI
- 10.1016/j.ebiom.2020.103157
- PMID
- 33418499
- PMCID
- PMC7804602
- NLM abbreviation
- EBioMedicine
- ISSN
- 2352-3964
- eISSN
- 2352-3964
- Publisher
- Elsevier B.V
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health; DOI: 10.13039/100000001, name: National Science Foundation
- Language
- English
- Date published
- 01/2021
- Academic Unit
- Epidemiology; Injury Prevention Research Center; Internal Medicine
- Record Identifier
- 9984364396302771
Metrics
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