Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 981-994 |
| Number of pages | 14 |
| Journal | Journal of the American Society of Nephrology : JASN |
| Volume | 28 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2017 |
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SOS2 and ACP1 Loci Identified through Large-Scale Exome Chip Analysis Regulate Kidney Development and Function. / Li, M; Li, Y; Weeks, O; Mijatovic, V; Teumer, A; Huffman, JE; Tromp, G; Fuchsberger, C; Gorski, M; Lyytikäinen, LP; Nutile, T; Sedaghat, S; Sorice, R; Tin, A; Yang, Q; Ahluwalia, TS; Arking, DE; Bihlmeyer, NA; Böger, CA; Carroll, RJ; Chasman, DI; Cornelis, MC; Dehghan, A; Faul, JD; Feitosa, MF; Gambaro, Giovanni; Gasparini, P; Giulianini, F; Heid, I; Huang, J; Imboden, M; Jackson, AU; Jeff, J; Jhun, MA; Katz, R; Kifley, A; Kilpeläinen, TO; Kumar, A; Laakso, M; Li-Gao, R; Lohman, K; Lu, Y; Mägi, R; Malerba, G; Mihailov, E; Mohlke, KL; Mook-Kanamori, DO; Robino, A; Ruderfer, D; Salvi, E; Schick, UM; Schulz, CA; Smith, AV; Smith, JA; Traglia, M; Yerges-Armstrong, LM; Zhao, W; Goodarzi, MO; Kraja, AT; Liu, C; Wessel, J; Group, CHARGE Glycemic-T2D Working; Group, CHARGE Blood Pressure Working; Boerwinkle, E; Borecki, IB; Bork-Jensen, J; Bottinger, EP; Braga, Daniele; Brandslund, I; Brody, JA; Campbell, A; Carey, DJ; Christensen, C; Coresh, J; Crook, E; Curhan, GC; Cusi, D; de Boer, IH; de Vries, AP; Denny, JC; Devuyst, O; Dreisbach, AW; Endlich, K; Esko, T; Franco, OH; Fulop, T; Gerhard, GS; Glümer, C; Gottesman, O; Grarup, N; Gudnason, V; Hansen, T; Harris, TB; Hayward, C; Hocking, L; Hofman, A; Hu, FB; Husemoen, LL; Jackson, RD; Jørgensen, T; Jørgensen, ME; Kähönen, M; Kardia, SL; König, W; Kooperberg, C; Kriebel, J; Launer, LJ; Lauritzen, T; Lehtimäki, T; Levy, D; Linksted, P; Linneberg, A; Liu, Y; Loos, RJ; Lupo, A; Meisinger, C; Melander, O; Metspalu, A; Mitchell, P; Nauck, M; Nürnberg, P; Orho-Melander, M; Parsa, A; Pedersen, O; Peters, A; Peters, U; Polasek, O; Porteous, D; Probst-Hensch, NM; Psaty, BM; Qi, L; Raitakari, OT; Reiner, AP; Rettig, R; Ridker, PM; Rivadeneira, F; Rossouw, JE; Schmidt, F; Siscovick, D; Soranzo, N; Strauch, K; Toniolo, D; Turner, ST; Uitterlinden, AG; Ulivi, S; Velayutham, D; Völker, U; Völzke, H; Waldenberger, M; Wang, JJ; Weir, DR; Witte, D; Kuivaniemi, H; Fox, CS; Franceschini, N; Goessling, W; Köttgen, A; Chu, AY.
In: Journal of the American Society of Nephrology : JASN, Vol. 28, No. 3, 2017, p. 981-994.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - SOS2 and ACP1 Loci Identified through Large-Scale Exome Chip Analysis Regulate Kidney Development and Function
AU - Li, M
AU - Li, Y
AU - Weeks, O
AU - Mijatovic, V
AU - Teumer, A
AU - Huffman, JE
AU - Tromp, G
AU - Fuchsberger, C
AU - Gorski, M
AU - Lyytikäinen, LP
AU - Nutile, T
AU - Sedaghat, S
AU - Sorice, R
AU - Tin, A
AU - Yang, Q
AU - Ahluwalia, TS
AU - Arking, DE
AU - Bihlmeyer, NA
AU - Böger, CA
AU - Carroll, RJ
AU - Chasman, DI
AU - Cornelis, MC
AU - Dehghan, A
AU - Faul, JD
AU - Feitosa, MF
AU - Gambaro, Giovanni
AU - Gasparini, P
AU - Giulianini, F
AU - Heid, I
AU - Huang, J
AU - Imboden, M
AU - Jackson, AU
AU - Jeff, J
AU - Jhun, MA
AU - Katz, R
AU - Kifley, A
AU - Kilpeläinen, TO
AU - Kumar, A
AU - Laakso, M
AU - Li-Gao, R
AU - Lohman, K
AU - Lu, Y
AU - Mägi, R
AU - Malerba, G
AU - Mihailov, E
AU - Mohlke, KL
AU - Mook-Kanamori, DO
AU - Robino, A
AU - Ruderfer, D
AU - Salvi, E
AU - Schick, UM
AU - Schulz, CA
AU - Smith, AV
AU - Smith, JA
AU - Traglia, M
AU - Yerges-Armstrong, LM
AU - Zhao, W
AU - Goodarzi, MO
AU - Kraja, AT
AU - Liu, C
AU - Wessel, J
AU - Group, CHARGE Glycemic-T2D Working
AU - Group, CHARGE Blood Pressure Working
AU - Boerwinkle, E
AU - Borecki, IB
AU - Bork-Jensen, J
AU - Bottinger, EP
AU - Braga, Daniele
AU - Brandslund, I
AU - Brody, JA
AU - Campbell, A
AU - Carey, DJ
AU - Christensen, C
AU - Coresh, J
AU - Crook, E
AU - Curhan, GC
AU - Cusi, D
AU - de Boer, IH
AU - de Vries, AP
AU - Denny, JC
AU - Devuyst, O
AU - Dreisbach, AW
AU - Endlich, K
AU - Esko, T
AU - Franco, OH
AU - Fulop, T
AU - Gerhard, GS
AU - Glümer, C
AU - Gottesman, O
AU - Grarup, N
AU - Gudnason, V
AU - Hansen, T
AU - Harris, TB
AU - Hayward, C
AU - Hocking, L
AU - Hofman, A
AU - Hu, FB
AU - Husemoen, LL
AU - Jackson, RD
AU - Jørgensen, T
AU - Jørgensen, ME
AU - Kähönen, M
AU - Kardia, SL
AU - König, W
AU - Kooperberg, C
AU - Kriebel, J
AU - Launer, LJ
AU - Lauritzen, T
AU - Lehtimäki, T
AU - Levy, D
AU - Linksted, P
AU - Linneberg, A
AU - Liu, Y
AU - Loos, RJ
AU - Lupo, A
AU - Meisinger, C
AU - Melander, O
AU - Metspalu, A
AU - Mitchell, P
AU - Nauck, M
AU - Nürnberg, P
AU - Orho-Melander, M
AU - Parsa, A
AU - Pedersen, O
AU - Peters, A
AU - Peters, U
AU - Polasek, O
AU - Porteous, D
AU - Probst-Hensch, NM
AU - Psaty, BM
AU - Qi, L
AU - Raitakari, OT
AU - Reiner, AP
AU - Rettig, R
AU - Ridker, PM
AU - Rivadeneira, F
AU - Rossouw, JE
AU - Schmidt, F
AU - Siscovick, D
AU - Soranzo, N
AU - Strauch, K
AU - Toniolo, D
AU - Turner, ST
AU - Uitterlinden, AG
AU - Ulivi, S
AU - Velayutham, D
AU - Völker, U
AU - Völzke, H
AU - Waldenberger, M
AU - Wang, JJ
AU - Weir, DR
AU - Witte, D
AU - Kuivaniemi, H
AU - Fox, CS
AU - Franceschini, N
AU - Goessling, W
AU - Köttgen, A
AU - Chu, AY
PY - 2017
Y1 - 2017
N2 - Genome-wide association studies have identified > 50 common variants associated with kidney function, but these variants do not fully explain the variation in eGFR. We performed a two-stage meta-analysis of associations between genotypes from the Illumina exome array and eGFR on the basis of serum creatinine (eGFRcrea) among participants of European ancestry from the CKDGen Consortium (nStage1: 111,666; nStage2: 48,343). In single-variant analyses, we identified single nucleotide polymorphisms at seven new loci associated with eGFRcrea (PPM1J, EDEM3, ACP1, SPEG, EYA4, CYP1A1, and ATXN2L; PStage1 <3.7×10-7), of which most were common and annotated as nonsynonymous variants. Gene-based analysis identified associations of functional rare variants in three genes with eGFRcrea, including a novel association with the SOS Ras/Rho guanine nucleotide exchange factor 2 gene, SOS2 (P=5.4×10-8 by sequence kernel association test). Experimental follow-up in zebrafish embryos revealed changes in glomerular gene expression and renal tubule morphology in the embryonic kidney of acp1- and sos2-knockdowns. These developmental abnormalities associated with altered blood clearance rate and heightened prevalence of edema. This study expands the number of loci associated with kidney function and identifies novel genes with potential roles in kidney formation. Copyright © 2017 by the American Society of Nephrology.
AB - Genome-wide association studies have identified > 50 common variants associated with kidney function, but these variants do not fully explain the variation in eGFR. We performed a two-stage meta-analysis of associations between genotypes from the Illumina exome array and eGFR on the basis of serum creatinine (eGFRcrea) among participants of European ancestry from the CKDGen Consortium (nStage1: 111,666; nStage2: 48,343). In single-variant analyses, we identified single nucleotide polymorphisms at seven new loci associated with eGFRcrea (PPM1J, EDEM3, ACP1, SPEG, EYA4, CYP1A1, and ATXN2L; PStage1 <3.7×10-7), of which most were common and annotated as nonsynonymous variants. Gene-based analysis identified associations of functional rare variants in three genes with eGFRcrea, including a novel association with the SOS Ras/Rho guanine nucleotide exchange factor 2 gene, SOS2 (P=5.4×10-8 by sequence kernel association test). Experimental follow-up in zebrafish embryos revealed changes in glomerular gene expression and renal tubule morphology in the embryonic kidney of acp1- and sos2-knockdowns. These developmental abnormalities associated with altered blood clearance rate and heightened prevalence of edema. This study expands the number of loci associated with kidney function and identifies novel genes with potential roles in kidney formation. Copyright © 2017 by the American Society of Nephrology.
U2 - 10.1681/ASN.2016020131
DO - 10.1681/ASN.2016020131
M3 - Article
VL - 28
SP - 981
EP - 994
JO - Journal of the American Society of Nephrology : JASN
JF - Journal of the American Society of Nephrology : JASN
SN - 1046-6673
IS - 3
ER -