PMID- 31451708

OWN - NLM
STAT- In-Data-Review
LR - 20190829
IS - 2041-1723 (Electronic)
IS - 2041-1723 (Linking)
VI - 10
IP - 1
DP - 2019 Aug 26
TI - Mapping eGFR loci to the renal transcriptome and phenome in the VA Million
Veteran Program.
PG - 3842
LID - 10.1038/s41467-019-11704-w [doi]
AB - Chronic kidney disease (CKD), defined by low estimated glomerular filtration
rate
(eGFR), contributes to global morbidity and mortality. Here we conduct a
transethnic Genome-Wide Association Study of eGFR in 280,722 participants of
the
Million Veteran Program (MVP), with replication in 765,289 participants from
the
Chronic Kidney Disease Genetics (CKDGen) Consortium. We identify 82
previously
unreported variants, confirm 54 loci, and report interesting findings
including
association of the sickle cell allele of betaglobin among non-Hispanic
blacks.
Our transcriptome-wide association study of kidney function in healthy kidney
tissue identifies 36 previously unreported and nine known genes, and maps
gene
expression to renal cell types. In a Phenome-Wide Association Study in
192,868
MVP participants using a weighted genetic score we detect associations with
CKD
stages and complications and kidney stones. This investigation reinterprets
the
genetic architecture of kidney function to identify the gene, tissue, and
anatomical context of renal homeostasis and the clinical consequences of
dysregulation.
FAU - Hellwege, Jacklyn N
AU - Hellwege JN
AUID- ORCID: http://orcid.org/0000-0001-7479-0920
AD - Biomedical Laboratory Research and Development, Tennessee Valley Healthcare
System (626)/Vanderbilt University, Nashville, TN, USA.
AD - Division of Genetic Medicine, Department of Medicine, Vanderbilt Genetics
Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
FAU - Velez Edwards, Digna R
AU - Velez Edwards DR
AD - Biomedical Laboratory Research and Development, Tennessee Valley Healthcare
System (626)/Vanderbilt University, Nashville, TN, USA.
AD - Department of Obstetrics & Gynecology, Vanderbilt Genetics Institute,
Vanderbilt
Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN,
USA.
AD - Department of Biomedical Informatics, Vanderbilt University Medical Center,
Nashville, TN, USA.
FAU - Giri, Ayush
AU - Giri A
AUID- ORCID: http://orcid.org/0000-0002-7786-4670
AD - Biomedical Laboratory Research and Development, Tennessee Valley Healthcare
System (626)/Vanderbilt University, Nashville, TN, USA.
AD - Department of Obstetrics & Gynecology, Vanderbilt Genetics Institute,
Vanderbilt
Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN,
USA.
FAU - Qiu, Chengxiang
AU - Qiu C
AD - Department of Medicine, Renal Electrolyte and Hypertension Division,
University
of Pennsylvania, Philadelphia, PA, USA.
FAU - Park, Jihwan
AU - Park J
AUID- ORCID: http://orcid.org/0000-0002-5728-912X
AD - Department of Medicine, Renal Electrolyte and Hypertension Division,
University
of Pennsylvania, Philadelphia, PA, USA.
FAU - Torstenson, Eric S
AU - Torstenson ES
AD - Biomedical Laboratory Research and Development, Tennessee Valley Healthcare
System (626)/Vanderbilt University, Nashville, TN, USA.
AD - Division of Epidemiology, Department of Medicine, Vanderbilt Genetics
Institute,
Vanderbilt University Medical Center, Nashville, TN, USA.
FAU - Keaton, Jacob M
AU - Keaton JM
AD - Biomedical Laboratory Research and Development, Tennessee Valley Healthcare
System (626)/Vanderbilt University, Nashville, TN, USA.
AD - Division of Epidemiology, Department of Medicine, Vanderbilt Genetics
Institute,
Vanderbilt University Medical Center, Nashville, TN, USA.
FAU - Wilson, O D
AU - Wilson OD
AD - Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt
University Medical Center, Nashville, TN, USA.
FAU - Robinson-Cohen, Cassianne
AU - Robinson-Cohen C
AD - Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt
University Medical Center, Nashville, TN, USA.
FAU - Chung, Cecilia P
AU - Chung CP
AD - Biomedical Laboratory Research and Development, Tennessee Valley Healthcare
System (626)/Vanderbilt University, Nashville, TN, USA.
AD - Divisions of Rheumatology and Clinical Pharmacology, Department of Medicine,
Vanderbilt University Medical Center, Nashville, TN, USA.
FAU - Roumie, Christianne L
AU - Roumie CL
AD - Veteran Affairs Administration Tennessee Valley VA Health Care System
Geriatric
Research Education Clinical Center (GRECC), Nashville, TN, USA.
AD - Department of Medicine, Vanderbilt University Medical Center, Nashville, TN,
USA.
FAU - Klarin, Derek
AU - Klarin D
AUID- ORCID: http://orcid.org/0000-0002-4636-5780
AD - VA Boston Health Care System, Boston, MA, USA.
AD - Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical
School, Boston, MA, USA.
AD - Program in Medical and Population Genetics, Broad Institute of Harvard and
MIT,
Cambridge, MA, USA.
AD - Department of Surgery, Massachusetts General Hospital, Harvard Medical
School,
Boston, MA, USA.
FAU - Damrauer, Scott M
AU - Damrauer SM
AD - Department of Surgery, Corporal Michael Crescenz VA Medical Center,
Philadelphia,
PA, USA.
AD - Department of Surgery, Perelman School of Medicine, University of
Pennsylvania,
Philadelphia, PA, USA.
FAU - DuVall, Scott L
AU - DuVall SL
AUID- ORCID: http://orcid.org/0000-0002-4898-3865
AD - VA Salt Lake City Health Care System, Salt Lake City, UT, USA.
AD - University of Utah School of Medicine, Salt Lake City, UT, USA.
FAU - Siew, Edward
AU - Siew E
AD - Department of Medicine, Vanderbilt University Medical Center, Nashville, TN,
USA.
FAU - Akwo, Elvis A
AU - Akwo EA
AD - Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt
University Medical Center, Nashville, TN, USA.
FAU - Wuttke, Matthias
AU - Wuttke M
AUID- ORCID: http://orcid.org/0000-0003-3420-5082
AD - Institute of Genetic Epidemiology, Department of Biometry, Epidemiology and
Medical Bioinformatics, Faculty of Medicine and Medical Centre-University of
Freiburg, Freiburg, Germany.
FAU - Gorski, Mathias
AU - Gorski M
AUID- ORCID: http://orcid.org/0000-0002-9103-5860
AD - Department of Genetic Epidemiology, Institute of Epidemiology and Preventive
Medicine, University of Regensburg, Regensburg, Germany.
AD - Department of Nephrology, University Hospital Regensburg, Regensburg,
Germany.
FAU - Li, Man
AU - Li M
AUID- ORCID: http://orcid.org/0000-0002-3839-0281
AD - VA Boston Health Care System, Boston, MA, USA.
AD - Division of Nephrology, Department of Internal Medicine, University of Utah
School of Medicine, Salt Lake City, UT, USA.
FAU - Li, Yong
AU - Li Y
AUID- ORCID: http://orcid.org/0000-0003-2651-8791
AD - Institute of Genetic Epidemiology, Department of Biometry, Epidemiology and
Medical Bioinformatics, Faculty of Medicine and Medical Centre-University of
Freiburg, Freiburg, Germany.
FAU - Gaziano, J Michael
AU - Gaziano JM
AD - Program in Medical and Population Genetics, Broad Institute of Harvard and
MIT,
Cambridge, MA, USA.
AD - Department of Surgery, Massachusetts General Hospital, Harvard Medical
School,
Boston, MA, USA.
AD - Massachusetts Veterans Epidemiology Research and Information Center
(MAVERIC), VA
Boston Healthcare System, Boston, MA, USA.
FAU - Wilson, Peter W F
AU - Wilson PWF
AD - Atlanta VA Medical Center, Atlanta, GA, USA.
AD - Emory Clinical Cardiovascular Research Institute, Atlanta, GA, USA.
FAU - Tsao, Philip S
AU - Tsao PS
AD - VA Palo Alto Health Care System, Palo Alto, CA, USA.
AD - Department of Medicine, Stanford University School of Medicine, Stanford, CA,
USA.
FAU - O'Donnell, Christopher J
AU - O'Donnell CJ
AD - VA Boston Health Care System, Boston, MA, USA.
AD - Section of Cardiology and Department of Medicine, Brigham and Women's
Hospital,
Harvard Medical School, Boston, MA, USA.
FAU - Kovesdy, Csaba P
AU - Kovesdy CP
AD - Nephrology Section, Memphis VA Medical Center, Memphis, TN, USA.
AD - Division of Nephrology, University of Tennessee Health Science Center,
Memphis,
TN, USA.
FAU - Pattaro, Cristian
AU - Pattaro C
AUID- ORCID: http://orcid.org/0000-0002-4119-0109
AD - Institute for Biomedicine, Eurac Research, Bolzano, Italy.
FAU - Kottgen, Anna
AU - Kottgen A
AUID- ORCID: http://orcid.org/0000-0002-4671-3714
AD - Institute of Genetic Epidemiology, Department of Biometry, Epidemiology and
Medical Bioinformatics, Faculty of Medicine and Medical Centre-University of
Freiburg, Freiburg, Germany.
AD - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health,
Baltimore, MD, USA.
FAU - Susztak, Katalin
AU - Susztak K
AUID- ORCID: http://orcid.org/0000-0002-1005-3726
AD - Department of Medicine, Renal Electrolyte and Hypertension Division,
University
of Pennsylvania, Philadelphia, PA, USA.
FAU - Edwards, Todd L
AU - Edwards TL
AUID- ORCID: http://orcid.org/0000-0003-4318-6119
AD - Biomedical Laboratory Research and Development, Tennessee Valley Healthcare
System (626)/Vanderbilt University, Nashville, TN, USA.
todd.l.edwards@vanderbilt.edu.
AD - Division of Epidemiology, Department of Medicine, Vanderbilt Genetics
Institute,
Vanderbilt University Medical Center, Nashville, TN, USA.
todd.l.edwards@vanderbilt.edu.
FAU - Hung, Adriana M
AU - Hung AM
AUID- ORCID: http://orcid.org/0000-0002-3203-1608
AD - Biomedical Laboratory Research and Development, Tennessee Valley Healthcare
System (626)/Vanderbilt University, Nashville, TN, USA.
adriana.hung@vanderbilt.edu.
AD - Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt
 University Medical Center, Nashville, TN, USA. adriana.hung@vanderbilt.edu.
LA - eng
GR - K12 HD043483/HD/NICHD NIH HHS/United States
GR - K01DK109019/U.S. Department of Health & Human Services | NIH | National
Institute
of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes
&
Digestive & Kidney Diseases)
GR - R01DK076077/U.S. Department of Health & Human Services | NIH | National
Institute
of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes
&
Digestive & Kidney Diseases)
GR - R01DK105821/U.S. Department of Health & Human Services | NIH | National
Institute
of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes
&
Digestive & Kidney Diseases)
GR - DP3DK108220/U.S. Department of Health & Human Services | NIH | National
Institute
of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes
&
Digestive & Kidney Diseases)
GR - DFG CRC 1140/Deutsche Forschungsgemeinschaft (German Research Foundation)
GR - DFG BO-3815/4-1/Deutsche Forschungsgemeinschaft (German Research Foundation)
GR - NAKSYS/Else Kroner-Fresenius-Stiftung (Else Kroner-Fresenius Foundation)
GR - I01-BX002641/U.S. Department of Veterans Affairs (Department of Veterans
Affairs)
PT - Journal Article
DEP - 20190826
PL - England
TA - Nat Commun
JT - Nature communications
JID - 101528555
SB - IM
PMC - PMC6710266
EDAT- 2019/08/28 06:00
MHDA- 2019/08/28 06:00
CRDT- 2019/08/28 06:00
PHST- 2019/01/15 00:00 [received]
PHST- 2019/07/23 00:00 [accepted]
PHST- 2019/08/28 06:00 [entrez]
PHST- 2019/08/28 06:00 [pubmed]
PHST- 2019/08/28 06:00 [medline]
AID - 10.1038/s41467-019-11704-w [doi]
AID - 10.1038/s41467-019-11704-w [pii]
PST - epublish
SO - Nat Commun. 2019 Aug 26;10(1):3842. doi: 10.1038/s41467-019-11704-w.