Genome-wide study investigating effector genes and polygenic prediction for kidney function in persons with ancestry from Africa and the Americas

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  • Odessica Hughes
  • Amy R. Bentley
  • Charles E. Breeze
  • Francois Aguet
  • Xiaoguang Xu
  • Girish Nadkarni
  • Quan Sun
  • Bridget M. Lin
  • Thomas Gilliland
  • Mariah C. Meyer
  • Jiawen Du
  • Laura M. Raffield
  • Holly Kramer
  • Robert W. Morton
  • Mateus H. Gouveia
  • Elizabeth G. Atkinson
  • Adan Valladares-Salgado
  • Niels Wacher-Rodarte
  • Nicole D. Dueker
  • Xiuqing Guo
  • Yang Hai
  • Adebowale Adeyemo
  • Lyle G. Best
  • Jianwen Cai
  • Guanjie Chen
  • Michael Chong
  • Ayo Doumatey
  • James Eales
  • Mark O. Goodarzi
  • Eli Ipp
  • Marguerite Ryan Irvin
  • Minzhi Jiang
  • Alana C. Jones
  • Charles Kooperberg
  • Jose E. Krieger
  • Ethan M. Lange
  • Matthew B. Lanktree
  • James P. Lash
  • Paulo A. Lotufo
  • Vy Thi Ha My
  • Jesús Peralta-Romero
  • Lihong Qi
  • Leslie J. Raffel
  • Stephen S. Rich
  • Erik J. Rodriquez
  • Eduardo Tarazona-Santos
  • Kent D. Taylor
  • Jason G. Umans
  • Jia Wen
  • Bessie A. Young
  • Zhi Yu
  • Ying Zhang
  • Yii Der Ida Chen
  • Tanja Rundek
  • Jerome I. Rotter
  • Miguel Cruz
  • Myriam Fornage
  • Maria Fernanda Lima-Costa
  • Alexandre C. Pereira
  • Guillaume Paré
  • Pradeep Natarajan
  • Shelley A. Cole
  • April P. Carson
  • Leslie A. Lange
  • Yun Li
  • Eliseo J. Perez-Stable
  • Ron Do
  • Fadi J. Charchar
  • Maciej Tomaszewski
  • Josyf C. Mychaleckyj
  • Charles Rotimi
  • Andrew P. Morris
  • Nora Franceschini

Chronic kidney disease is a leading cause of death and disability globally and impacts individuals of African ancestry (AFR) or with ancestry in the Americas (AMS) who are under-represented in genome-wide association studies (GWASs) of kidney function. To address this bias, we conducted a large meta-analysis of GWASs of estimated glomerular filtration rate (eGFR) in 145,732 AFR and AMS individuals. We identified 41 loci at genome-wide significance (p < 5 × 10−8), of which two have not been previously reported in any ancestry group. We integrated fine-mapped loci with epigenomic and transcriptomic resources to highlight potential effector genes relevant to kidney physiology and disease, and reveal key regulatory elements and pathways involved in renal function and development. We demonstrate the varying but increased predictive power offered by a multi-ancestry polygenic score for eGFR and highlight the importance of population diversity in GWASs and multi-omics resources to enhance opportunities for clinical translation for all.

OriginalsprogEngelsk
Artikelnummer100468
TidsskriftCell Genomics
Vol/bind4
Udgave nummer1
Antal sider13
ISSN2666-979x
DOI
StatusUdgivet - 2024

Bibliografisk note

Funding Information:
Genetics of Latinos Diabetic Retinopathy (GOLDR): GOLDR was supported in part by the Genetics of Latinos Diabetic Retinopathy (GOLDR) Study grant EY14684 . The provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences , CTSI grant, UL1TR001881 , and the National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) grant DK063491 to the Southern California Diabetes Research Center .

Funding Information:
African American Diabetes Mellitus Study (AADM): the study was supported in part by the NIH Intramural Research Program in the Center for Research on Genomics and Global Health (CRGGH). The CRGGH is supported by the NHGRI , the National Institute of Diabetes and Digestive and Kidney Diseases , and the Office of the Director at the NIH ( 1ZIAHG200362 ). Support for participant recruitment and initial genetic studies of the AADM study was provided by NIH grant no. 3T37TW00041-03S2 from the Office of Research on Minority Health .

Funding Information:
Mexico City Studies (MC): in Mexico, this work was supported by the Fondo Sectorial de Investigación en Salud y Seguridad Social (SSA/IMSS/ISSSTE-CONACYT, project 150352), Temas Prioritarios de Salud Instituto Mexicano del Seguro Social ( 2014-FIS/IMSS/PROT/PRIO/14/34 ), and the Fundación IMSS . We thank Jorge Gutierrez Cuevas, Jaime Gómez Zamudio, and Araceli Méndez Padrón for technical support. In Canada, computations were performed on the GPC supercomputer at the SciNet HPC Consortium. SciNet is funded by: the Calgary Foundation for Innovation under the auspices of Compute Canada; the Government of Ontario, Ontario Research Fund – Research Excellence ; and the University of Toronto . E.J.P. was supported by the Canadian Institutes of Health Research and the Banting and Best Diabetes Centre, University of Toronto .

Funding Information:
Howard University Family Study (HUFS): HUFS was supported by NIH grants S06GM008016-320107 to C.R. and S06GM008016-380111 to A.A. We thank the participants of the study, for which enrollment was carried out at the Howard University General Clinical Research Center, supported by NIH grant 2M01RR010284 .

Funding Information:
Hispanic Community Health Study and Study of Latinos (HCHS/SOL): HCHS/SOL was carried out as a collaborative study supported by contracts from the NHLBI to the University of North Carolina ( N01-HC-65233 ), University of Miami ( N01-HC-65234 ), Albert Einstein College of Medicine ( N01-HC-65235 ), Northwestern University ( N01-HC-65236 ), and San Diego State University ( N01-HC-65237 ). The following contribute to the HCHS/SOL through a transfer of funds to the NHLBI : National Center on Minority Health and Health Disparities , the National Institute of Deafness and Other Communications Disorders , the National Institute of Dental and Craniofacial Research (NIDCR), the National Institute of Diabetes and Digestive and Kidney Diseases , the National Institute of Neurological Disorders and Stroke , and the Office of Dietary Supplements . The Genetic Analysis Center at the University of Washington was supported by NHLBI and NIDCR contracts ( HHSN268201300005C AM03 and MOD03 ).

Funding Information:
Atherosclerosis Risk in Communities Study (ARIC): the ARIC study has been funded in whole or in part with Federal funds from the NHLBI ,NIH, Department of Health and Human Services , under contract numbers HHSN268201700001I , HHSN268201700002I , HHSN268201700003I , HHSN268201700004I , and HHSN268201700005I . The authors thank the staff and participants of the ARIC study for their important contributions. Funding for the GENEVA substudy was provided by NHGRI grant U01HG004402 (E. Boerwinkle). Access through dbGAP for ARIC (phs000280.v7).

Funding Information:
BioME Biobank (BIOME): the Mount Sinai BioME Biobank is supported by The Andrea and Charles Bronfman Philanthropies .

Funding Information:
Bambui (Brazil) Cohort Study of Ageing (BAMBUI): the EPIGEN-Brazil Initiative is funded by the Brazilian Ministry of Health (Department of Science and Technology from the Secretaria de Ciência, Tecnologia e Insumos Estratégicos) through Financiadora de Estudos e Projetos. This project was supported by the Intramural Research Program of the NHGRI , NIH, through the Center for Research on Genomics and Global Health (CRGGH).

Funding Information:
Multi-Ethnic Study of Atherosclerosis (MESA): MESA and the MESA SHARe projects are conducted and supported by the NHLBI in collaboration with MESA investigators. Support for MESA is provided by contracts 75N92020D00001 , HHSN268201500003I , N01-HC-95159 , 75N92020D00005 , N01-HC-95160 , 75N92020D00002 , N01-HC-95161 , 75N92020D00003 , N01-HC-95162 , 75N92020D00006 , N01-HC-95163 , 75N92020D00004 , N01-HC-95164 , 75N92020D00007 , N01-HC-95165 , N01-HC-95166 , N01-HC-95167 , N01-HC-95168 , N01-HC-95169 , UL1-TR-000040 , UL1-TR-001079 , and UL1-TR-001420 , UL1TR001881 , DK063491 , and R01HL105756 . Funding for SHARe genotyping was provided by NHLBI Contract N02-HL-64278 . Genotyping was performed at Affymetrix (Santa Clara, CA) and the Broad Institute of Harvard and MIT (Boston, MA) using the Affymetrix Genome-Wide Human SNP Array 6.0. MESA Family is conducted and supported by the NHLBI in collaboration with MESA investigators. Support is provided by grants and contracts R01HL071051, R01HL071205, R01HL071250, R01HL071251, R01HL071258, R01HL071259, UL1TR001881, and DK063491, and by the National Center for Research Resources , grant UL1RR033176 . The authors thank the other investigators, the staff, and the participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutes can be found at http://www.mesa-nhlbi.org .

Funding Information:
Coronary Artery Risk Development in Young Adults Study (CARDIA): CARDIA is conducted and supported by the NHLBI in collaboration with the University of Alabama at Birmingham ( HHSN268201800005I and HHSN268201800007I ), Northwestern University ( HHSN268201800003I ), University of Minnesota ( HHSN268201800006I ), and Kaiser Foundation Research Institute ( HHSN268201800004I ). Genotyping was funded as part of the NHLBI Candidate-gene Association Resource ( N01-HC-65226 ) and the NHGRI Gene Environment Association Studies ( GENEVA ) ( U01-HG004729 , U01-HG04424 , and U01-HG004446 ).

Funding Information:
Mexican American Hypertension and Insulin Resistance (HTNIR): this work was supported by the NHLBI (grant HL55005 ), the National Institutes of Health National Center for Research Resources , General Clinical Research Center (grants RR00425 to RR00430 , M01-RR00865 , M01-RR00043 , M01-RR00425 , and CA42710 ). The authors thank the families for their participation in this study.

Funding Information:
Women’s Health Initiative (WHI): the WHI program is funded by the NHLBI through contracts HHSN268201600018C , HHSN268201600001C , HHSN268201600002C , HHSN268201600003C , and HHSN268201600004C . We thank the WHI investigators and staff for their dedication, and the study participants for making the program possible. A full listing of WHI investigators can be found at: http://www.whi.org/researchers/Documents%20%20Write%20a%20Paper/WHI%20Investigator%20Long%20List.pdf .

Funding Information:
This study was supported by National Institutes of Health (NIH) grants R01- DK117445 and R01- MD012765 (to N.F. and A.P.M.), U01-DK130044, R01-HL163972 and K26-DK138425 (to N.F.), R01- HL142711 , R01- HL127564 , and U01- HG011719 (to P.N.), T32- HL125232 (to T.G.), K01- MH121659 (to E.G.A.), and R01- HL136666 (to M.R.I.) . C.E.B. was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH . R.W.M. was supported by a Canadian Institutes of Health Research Fellowship during the completion of this work. M.T. and Human Kidney Tissue Resource are supported by grants from the British Heart Foundation ( PG/17/35/33001 , PG/19/16/34270 , and PG/22/10957 ), Kidney Research UK ( RP_017_20180302 and RP_013_20190305 ), and by the NIHR Manchester Biomedical Research Centre ( NIHR203308 ). E.T.S. is supported by the Minas Gerais Research Agency ( FAPEMIG ) and the Brazilian National Research Council ( CNPq ). E.J.R. and E.J.P.-S. were supported by the Division of Intramural Research of the National Heart, Lung, and Blood Institute (NHLBI) and the National Institute on Minority Health and Health Disparities at the NIH . This work was supported in part by the Intramural Research Program of the National Human Genome Research Institute (NHGRI) (to A.R.B. and C.R.).

Funding Information:
Sea Islands Genetic Network: Reasons for Geographic and Racial Differences in Stroke (REGARDS): the REGARDS study is supported by a cooperative agreement U01 NS041588 from the National Institute of Neurological Disorders and Stroke, NIH, U.S. Department of Health and Human Services . The authors thank the other investigators, the staff, and the participants of the REGARDS study for their valuable contributions. A full list of participating REGARDS investigators and institutions can be found at http://www.regardsstudy.org .

Publisher Copyright:
© 2023 The Authors

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