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Genetic Predisposition for Renal Dysfunction and Incidence of CKD in the Malmö Diet and Cancer Study

Schulz, Christina Alexandra LU ; Engström, Gunnar LU ; Christensson, Anders LU ; Nilsson, Peter M. LU ; Melander, Olle LU and Orho-Melander, M. LU (2019) In Kidney International Reports 4(8). p.1143-1151
Abstract

Background: Genome-wide association studies (GWAS) have identified >50 single nucleotide polymorphisms (SNP) in association with estimated glomerular filtration rate (eGFR) and chronic kidney disease (CKD) but little is known about whether the combination of these SNPs may aid in prediction of future incidence of CKD in the population. Methods: We included 2301 participants with baseline eGFR ≥60 mL/min per 1.73 m2 from the Malmö Diet and Cancer Study–Cardiovascular Cohort. The eGFR was estimated during baseline (1991–1996) and after a mean follow-up of 16.6 years using the CKD–Epidemiology Collaboration 2009 creatinine equation. We combined 53 SNPs into a genetic risk score weighted by the effect size... (More)

Background: Genome-wide association studies (GWAS) have identified >50 single nucleotide polymorphisms (SNP) in association with estimated glomerular filtration rate (eGFR) and chronic kidney disease (CKD) but little is known about whether the combination of these SNPs may aid in prediction of future incidence of CKD in the population. Methods: We included 2301 participants with baseline eGFR ≥60 mL/min per 1.73 m2 from the Malmö Diet and Cancer Study–Cardiovascular Cohort. The eGFR was estimated during baseline (1991–1996) and after a mean follow-up of 16.6 years using the CKD–Epidemiology Collaboration 2009 creatinine equation. We combined 53 SNPs into a genetic risk score weighted by the effect size (wGRSCKD), and examined its association with incidence of CKD stage 3A (eGFR ≤60 mL/min per 1.73 m2). Results: At follow-up, 453 study participants were defined as having CKD stage 3A. We observed a strong association between wGRSCKD and eGFR at baseline (P = 6.5 × 10−8) and at the follow-up reexamination (P = 5.0 × 10−10). The odds ratio (OR) for incidence of CKD stage 3A was 1.25 per 1 SD increment in the wGRSCKD (95% confidence interval [CI]: 1.12–1.39) adjusting for potential confounders (sex, age, body mass index [BMI], baseline eGFR, fasting glucose, systolic blood pressure (SBP), antihypertensive treatment, smoking, follow-up time). Adding wGRSCKD on the top of traditional risk factors did not improve the C-statistics (P = 0.12), but the Net Reclassification-Improvement-Index was significantly improved (cNRI = 21.3%; 95% CI: 21.2–21.4; P < 0.0001). Conclusion: wGRSCKD was associated with a 25% increased incidence of CKD per 1 SD increment. Although the wGRSCKD did not improve the prediction model beyond clinical risk factors per se, the information of genetic predisposition may aid in reclassification of individuals into correct risk direction.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
CKD, eGFR, GRS, renal function
in
Kidney International Reports
volume
4
issue
8
pages
9 pages
publisher
Elsevier Inc.
external identifiers
  • scopus:85069738527
ISSN
2468-0249
DOI
10.1016/j.ekir.2019.05.003
language
English
LU publication?
yes
id
ccb5bbc0-a277-42b7-a5e8-102e0f7ea273
date added to LUP
2019-08-05 09:13:11
date last changed
2019-08-28 04:57:42
@article{ccb5bbc0-a277-42b7-a5e8-102e0f7ea273,
  abstract     = {<p>Background: Genome-wide association studies (GWAS) have identified &gt;50 single nucleotide polymorphisms (SNP) in association with estimated glomerular filtration rate (eGFR) and chronic kidney disease (CKD) but little is known about whether the combination of these SNPs may aid in prediction of future incidence of CKD in the population. Methods: We included 2301 participants with baseline eGFR ≥60 mL/min per 1.73 m<sup>2</sup> from the Malmö Diet and Cancer Study–Cardiovascular Cohort. The eGFR was estimated during baseline (1991–1996) and after a mean follow-up of 16.6 years using the CKD–Epidemiology Collaboration 2009 creatinine equation. We combined 53 SNPs into a genetic risk score weighted by the effect size (wGRS<sub>CKD</sub>), and examined its association with incidence of CKD stage 3A (eGFR ≤60 mL/min per 1.73 m<sup>2</sup>). Results: At follow-up, 453 study participants were defined as having CKD stage 3A. We observed a strong association between wGRS<sub>CKD</sub> and eGFR at baseline (P = 6.5 × 10<sup>−8</sup>) and at the follow-up reexamination (P = 5.0 × 10<sup>−10</sup>). The odds ratio (OR) for incidence of CKD stage 3A was 1.25 per 1 SD increment in the wGRS<sub>CKD</sub> (95% confidence interval [CI]: 1.12–1.39) adjusting for potential confounders (sex, age, body mass index [BMI], baseline eGFR, fasting glucose, systolic blood pressure (SBP), antihypertensive treatment, smoking, follow-up time). Adding wGRS<sub>CKD</sub> on the top of traditional risk factors did not improve the C-statistics (P = 0.12), but the Net Reclassification-Improvement-Index was significantly improved (cNRI = 21.3%; 95% CI: 21.2–21.4; P &lt; 0.0001). Conclusion: wGRS<sub>CKD</sub> was associated with a 25% increased incidence of CKD per 1 SD increment. Although the wGRS<sub>CKD</sub> did not improve the prediction model beyond clinical risk factors per se, the information of genetic predisposition may aid in reclassification of individuals into correct risk direction.</p>},
  author       = {Schulz, Christina Alexandra and Engström, Gunnar and Christensson, Anders and Nilsson, Peter M. and Melander, Olle and Orho-Melander, M.},
  issn         = {2468-0249},
  keyword      = {CKD,eGFR,GRS,renal function},
  language     = {eng},
  month        = {05},
  number       = {8},
  pages        = {1143--1151},
  publisher    = {Elsevier Inc.},
  series       = {Kidney International Reports},
  title        = {Genetic Predisposition for Renal Dysfunction and Incidence of CKD in the Malmö Diet and Cancer Study},
  url          = {http://dx.doi.org/10.1016/j.ekir.2019.05.003},
  volume       = {4},
  year         = {2019},
}