CUBN Is a Gene Locus for Albuminuria

CA Boger; MH Chen; A Tin; M Olden; A Koettgen; IH (Ian) Boer; C Fuchsberger; CM O'Seaghdha; C Pattaro; A Teumer; CT Liu; NL Glazer; M Li; JR O'Conne; T Tanaka; CA Peralta; Z Kutalik; J Luan; JH Zhao; SJ Hwang; E Akylbekova; H Kramer; P van der Harst; AV Smith; K Lohman; M de Andrade; C Hayward; B Kollerits; A Tonjes; T Aspelund; E Ingelsson; G Eiriksdottir; LJ (Lenore) Launer; TB Harris; AR Shuldiner; BD Mitchell; DE Arking; N Franceschini; E Boerwinkle; J Egan; D Hernandez; M O Reilly; RR Townsend; T Lumley; DS Siscovick; BM Psaty; B Kestenbaum; T Haritunians; S Bergmann; P Vollenweider; G Waeber; V Mooser; D Waterworth; AD Johnson; JC Florez; JB Meigs; XN Lu; ST Turner; EJ Atkinson; TS Leak; K Aasarod; F Skorpen; AC Syvanen; T Illig; J Baumert; W Koenig; BK Kramer; O Devuyst; JC Mychaleckyj; C Minelli; SJL Bakker; L Kedenko; B Paulweber; S Coassin; K Endlich; HK Kroemer; R Biffar; S Stracke; H Volzke; M Stumvol; R Magi; H Campbell; V Vitart; ND Hastie; V Gudnason; SLR Kardia; YM Liu; O Polasek; G Curhan; F Kronenberg; I Prokopenko; I Rudan; J Arnlov; S Hallan; G Navis; A Parsa; L Ferrucci; J Coresh; MG Shlipak; SB Bul; AD Paterson; HE Wichmann; NJ Wareham; RJF Loos; JI Rotter; PP Pramstaller; LA Cupples; JS Beckmann; QO Yang; IM Heid; R Rettig; AW Dreisbach; M Bochud; CS Fox; WHL Kao

CUBN Is a Gene Locus for Albuminuria

CA Boger, MH Chen, A Tin, M Olden, A Koettgen, IH (Ian) Boer, C Fuchsberger, CM O'Seaghdha, C Pattaro, A Teumer, CT Liu, NL Glazer, M Li, JR O'Conne, T Tanaka, CA Peralta, Z Kutalik, J Luan, JH Zhao, SJ HwangE Akylbekova, H Kramer, P van der Harst, AV Smith, K Lohman, M de Andrade, C Hayward, B Kollerits, A Tonjes, T Aspelund, E Ingelsson, G Eiriksdottir, LJ (Lenore) Launer, TB Harris, AR Shuldiner, BD Mitchell, DE Arking, N Franceschini, E Boerwinkle, J Egan, D Hernandez, M O Reilly, RR Townsend, T Lumley, DS Siscovick, BM Psaty, B Kestenbaum, T Haritunians, S Bergmann, P Vollenweider, G Waeber, V Mooser, D Waterworth, AD Johnson, JC Florez, JB Meigs, XN Lu, ST Turner, EJ Atkinson, TS Leak, K Aasarod, F Skorpen, AC Syvanen, T Illig, J Baumert, W Koenig, BK Kramer, O Devuyst, JC Mychaleckyj, C Minelli, SJL Bakker, L Kedenko, B Paulweber, S Coassin, K Endlich, HK Kroemer, R Biffar, S Stracke, H Volzke, M Stumvol, R Magi, H Campbell, V Vitart, ND Hastie, V Gudnason, SLR Kardia, YM Liu, O Polasek, G Curhan, F Kronenberg, I Prokopenko, I Rudan, J Arnlov, S Hallan, G Navis, A Parsa, L Ferrucci, J Coresh, MG Shlipak, SB Bul, AD Paterson, HE Wichmann, NJ Wareham, RJF Loos, JI Rotter, PP Pramstaller, LA Cupples, JS Beckmann, QO Yang, IM Heid, R Rettig, AW Dreisbach, M Bochud, CS Fox, WHL Kao

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Identification of genetic risk factors for albuminuria may alter strategies for early prevention of CKD progression, particularly among patients with diabetes. Little is known about the influence of common genetic variants on albuminuria in both general and diabetic populations. We performed a meta-analysis of data from 63,153 individuals of European ancestry with genotype information from genome-wide association studies (CKDGen Consortium) and from a large candidate gene study (CARe Consortium) to identify susceptibility loci for the quantitative trait urinary albumin-to-creatinine ratio (UACR) and the clinical diagnosis microalbuminuria. We identified an association between a missense variant (I2984V) in the CUBN gene, which encodes cubilin, and both UACR (P = 1.1 x 10(-11)) and microalbuminuria (P = 0.001). We observed similar associations among 6981 African Americans in the CARe Consortium. The associations between this variant and both UACR and microalbuminuria were significant in individuals of European ancestry regardless of diabetes status. Finally, this variant associated with a 41% increased risk for the development of persistent microalbuminuria during 20 years of follow-up among 1304 participants with type 1 diabetes in the prospective DCCT/EDIC Study. In summary, we identified a missense CUBN variant that associates with levels of albuminuria in both the general population and in individuals with diabetes.

Original language	Undefined/Unknown
Pages (from-to)	555-570
Number of pages	16
Journal	Journal of the American Society of Nephrology
Volume	22
Issue number	3
Publication status	Published - 2011

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Cite this

@article{dcdc764851ff416d9be7acabcfa4c1d3,

title = "CUBN Is a Gene Locus for Albuminuria",

abstract = "Identification of genetic risk factors for albuminuria may alter strategies for early prevention of CKD progression, particularly among patients with diabetes. Little is known about the influence of common genetic variants on albuminuria in both general and diabetic populations. We performed a meta-analysis of data from 63,153 individuals of European ancestry with genotype information from genome-wide association studies (CKDGen Consortium) and from a large candidate gene study (CARe Consortium) to identify susceptibility loci for the quantitative trait urinary albumin-to-creatinine ratio (UACR) and the clinical diagnosis microalbuminuria. We identified an association between a missense variant (I2984V) in the CUBN gene, which encodes cubilin, and both UACR (P = 1.1 x 10(-11)) and microalbuminuria (P = 0.001). We observed similar associations among 6981 African Americans in the CARe Consortium. The associations between this variant and both UACR and microalbuminuria were significant in individuals of European ancestry regardless of diabetes status. Finally, this variant associated with a 41% increased risk for the development of persistent microalbuminuria during 20 years of follow-up among 1304 participants with type 1 diabetes in the prospective DCCT/EDIC Study. In summary, we identified a missense CUBN variant that associates with levels of albuminuria in both the general population and in individuals with diabetes.",

author = "CA Boger and MH Chen and A Tin and M Olden and A Koettgen and Boer, {IH (Ian)} and C Fuchsberger and CM O'Seaghdha and C Pattaro and A Teumer and CT Liu and NL Glazer and M Li and JR O'Conne and T Tanaka and CA Peralta and Z Kutalik and J Luan and JH Zhao and SJ Hwang and E Akylbekova and H Kramer and {van der Harst}, P and AV Smith and K Lohman and {de Andrade}, M and C Hayward and B Kollerits and A Tonjes and T Aspelund and E Ingelsson and G Eiriksdottir and Launer, {LJ (Lenore)} and TB Harris and AR Shuldiner and BD Mitchell and DE Arking and N Franceschini and E Boerwinkle and J Egan and D Hernandez and {O Reilly}, M and RR Townsend and T Lumley and DS Siscovick and BM Psaty and B Kestenbaum and T Haritunians and S Bergmann and P Vollenweider and G Waeber and V Mooser and D Waterworth and AD Johnson and JC Florez and JB Meigs and XN Lu and ST Turner and EJ Atkinson and TS Leak and K Aasarod and F Skorpen and AC Syvanen and T Illig and J Baumert and W Koenig and BK Kramer and O Devuyst and JC Mychaleckyj and C Minelli and SJL Bakker and L Kedenko and B Paulweber and S Coassin and K Endlich and HK Kroemer and R Biffar and S Stracke and H Volzke and M Stumvol and R Magi and H Campbell and V Vitart and ND Hastie and V Gudnason and SLR Kardia and YM Liu and O Polasek and G Curhan and F Kronenberg and I Prokopenko and I Rudan and J Arnlov and S Hallan and G Navis and A Parsa and L Ferrucci and J Coresh and MG Shlipak and SB Bul and AD Paterson and HE Wichmann and NJ Wareham and RJF Loos and JI Rotter and PP Pramstaller and LA Cupples and JS Beckmann and QO Yang and IM Heid and R Rettig and AW Dreisbach and M Bochud and CS Fox and WHL Kao",

year = "2011",

language = "Undefined/Unknown",

volume = "22",

pages = "555--570",

journal = "Journal of the American Society of Nephrology : JASN",

issn = "1046-6673",

publisher = "American Society of Nephrology",

number = "3",

}

Boger, CA, Chen, MH, Tin, A, Olden, M, Koettgen, A, Boer, IH, Fuchsberger, C, O'Seaghdha, CM, Pattaro, C, Teumer, A, Liu, CT, Glazer, NL, Li, M, O'Conne, JR, Tanaka, T, Peralta, CA, Kutalik, Z, Luan, J, Zhao, JH, Hwang, SJ, Akylbekova, E, Kramer, H, van der Harst, P, Smith, AV, Lohman, K, de Andrade, M, Hayward, C, Kollerits, B, Tonjes, A, Aspelund, T, Ingelsson, E, Eiriksdottir, G, Launer, LJ, Harris, TB, Shuldiner, AR, Mitchell, BD, Arking, DE, Franceschini, N, Boerwinkle, E, Egan, J, Hernandez, D, O Reilly, M, Townsend, RR, Lumley, T, Siscovick, DS, Psaty, BM, Kestenbaum, B, Haritunians, T, Bergmann, S, Vollenweider, P, Waeber, G, Mooser, V, Waterworth, D, Johnson, AD, Florez, JC, Meigs, JB, Lu, XN, Turner, ST, Atkinson, EJ, Leak, TS, Aasarod, K, Skorpen, F, Syvanen, AC, Illig, T, Baumert, J, Koenig, W, Kramer, BK, Devuyst, O, Mychaleckyj, JC, Minelli, C, Bakker, SJL, Kedenko, L, Paulweber, B, Coassin, S, Endlich, K, Kroemer, HK, Biffar, R, Stracke, S, Volzke, H, Stumvol, M, Magi, R, Campbell, H, Vitart, V, Hastie, ND, Gudnason, V, Kardia, SLR, Liu, YM, Polasek, O, Curhan, G, Kronenberg, F, Prokopenko, I, Rudan, I, Arnlov, J, Hallan, S, Navis, G, Parsa, A, Ferrucci, L, Coresh, J, Shlipak, MG, Bul, SB, Paterson, AD, Wichmann, HE, Wareham, NJ, Loos, RJF, Rotter, JI, Pramstaller, PP, Cupples, LA, Beckmann, JS, Yang, QO, Heid, IM, Rettig, R, Dreisbach, AW, Bochud, M, Fox, CS & Kao, WHL 2011, 'CUBN Is a Gene Locus for Albuminuria', Journal of the American Society of Nephrology, vol. 22, no. 3, pp. 555-570.

TY - JOUR

T1 - CUBN Is a Gene Locus for Albuminuria

AU - Boger, CA

AU - Chen, MH

AU - Tin, A

AU - Olden, M

AU - Koettgen, A

AU - Boer, IH (Ian)

AU - Fuchsberger, C

AU - O'Seaghdha, CM

AU - Pattaro, C

AU - Teumer, A

AU - Liu, CT

AU - Glazer, NL

AU - Li, M

AU - O'Conne, JR

AU - Tanaka, T

AU - Peralta, CA

AU - Kutalik, Z

AU - Luan, J

AU - Zhao, JH

AU - Hwang, SJ

AU - Akylbekova, E

AU - Kramer, H

AU - van der Harst, P

AU - Smith, AV

AU - Lohman, K

AU - de Andrade, M

AU - Hayward, C

AU - Kollerits, B

AU - Tonjes, A

AU - Aspelund, T

AU - Ingelsson, E

AU - Eiriksdottir, G

AU - Launer, LJ (Lenore)

AU - Harris, TB

AU - Shuldiner, AR

AU - Mitchell, BD

AU - Arking, DE

AU - Franceschini, N

AU - Boerwinkle, E

AU - Egan, J

AU - Hernandez, D

AU - O Reilly, M

AU - Townsend, RR

AU - Lumley, T

AU - Siscovick, DS

AU - Psaty, BM

AU - Kestenbaum, B

AU - Haritunians, T

AU - Bergmann, S

AU - Vollenweider, P

AU - Waeber, G

AU - Mooser, V

AU - Waterworth, D

AU - Johnson, AD

AU - Florez, JC

AU - Meigs, JB

AU - Lu, XN

AU - Turner, ST

AU - Atkinson, EJ

AU - Leak, TS

AU - Aasarod, K

AU - Skorpen, F

AU - Syvanen, AC

AU - Illig, T

AU - Baumert, J

AU - Koenig, W

AU - Kramer, BK

AU - Devuyst, O

AU - Mychaleckyj, JC

AU - Minelli, C

AU - Bakker, SJL

AU - Kedenko, L

AU - Paulweber, B

AU - Coassin, S

AU - Endlich, K

AU - Kroemer, HK

AU - Biffar, R

AU - Stracke, S

AU - Volzke, H

AU - Stumvol, M

AU - Magi, R

AU - Campbell, H

AU - Vitart, V

AU - Hastie, ND

AU - Gudnason, V

AU - Kardia, SLR

AU - Liu, YM

AU - Polasek, O

AU - Curhan, G

AU - Kronenberg, F

AU - Prokopenko, I

AU - Rudan, I

AU - Arnlov, J

AU - Hallan, S

AU - Navis, G

AU - Parsa, A

AU - Ferrucci, L

AU - Coresh, J

AU - Shlipak, MG

AU - Bul, SB

AU - Paterson, AD

AU - Wichmann, HE

AU - Wareham, NJ

AU - Loos, RJF

AU - Rotter, JI

AU - Pramstaller, PP

AU - Cupples, LA

AU - Beckmann, JS

AU - Yang, QO

AU - Heid, IM

AU - Rettig, R

AU - Dreisbach, AW

AU - Bochud, M

AU - Fox, CS

AU - Kao, WHL

PY - 2011

Y1 - 2011

N2 - Identification of genetic risk factors for albuminuria may alter strategies for early prevention of CKD progression, particularly among patients with diabetes. Little is known about the influence of common genetic variants on albuminuria in both general and diabetic populations. We performed a meta-analysis of data from 63,153 individuals of European ancestry with genotype information from genome-wide association studies (CKDGen Consortium) and from a large candidate gene study (CARe Consortium) to identify susceptibility loci for the quantitative trait urinary albumin-to-creatinine ratio (UACR) and the clinical diagnosis microalbuminuria. We identified an association between a missense variant (I2984V) in the CUBN gene, which encodes cubilin, and both UACR (P = 1.1 x 10(-11)) and microalbuminuria (P = 0.001). We observed similar associations among 6981 African Americans in the CARe Consortium. The associations between this variant and both UACR and microalbuminuria were significant in individuals of European ancestry regardless of diabetes status. Finally, this variant associated with a 41% increased risk for the development of persistent microalbuminuria during 20 years of follow-up among 1304 participants with type 1 diabetes in the prospective DCCT/EDIC Study. In summary, we identified a missense CUBN variant that associates with levels of albuminuria in both the general population and in individuals with diabetes.

AB - Identification of genetic risk factors for albuminuria may alter strategies for early prevention of CKD progression, particularly among patients with diabetes. Little is known about the influence of common genetic variants on albuminuria in both general and diabetic populations. We performed a meta-analysis of data from 63,153 individuals of European ancestry with genotype information from genome-wide association studies (CKDGen Consortium) and from a large candidate gene study (CARe Consortium) to identify susceptibility loci for the quantitative trait urinary albumin-to-creatinine ratio (UACR) and the clinical diagnosis microalbuminuria. We identified an association between a missense variant (I2984V) in the CUBN gene, which encodes cubilin, and both UACR (P = 1.1 x 10(-11)) and microalbuminuria (P = 0.001). We observed similar associations among 6981 African Americans in the CARe Consortium. The associations between this variant and both UACR and microalbuminuria were significant in individuals of European ancestry regardless of diabetes status. Finally, this variant associated with a 41% increased risk for the development of persistent microalbuminuria during 20 years of follow-up among 1304 participants with type 1 diabetes in the prospective DCCT/EDIC Study. In summary, we identified a missense CUBN variant that associates with levels of albuminuria in both the general population and in individuals with diabetes.

M3 - Article

VL - 22

SP - 555

EP - 570

JO - Journal of the American Society of Nephrology : JASN

JF - Journal of the American Society of Nephrology : JASN

SN - 1046-6673

IS - 3

ER -