Genetic Predisposition for Renal Dysfunction and Incidence of CKD in the Malmö Diet and Cancer Study
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 fu...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2019-08-01
|
Series: | Kidney International Reports |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2468024919301846 |
id |
doaj-54deac374fc94a15b1955fae16a7ceda |
---|---|
record_format |
Article |
spelling |
doaj-54deac374fc94a15b1955fae16a7ceda2020-11-24T21:54:35ZengElsevierKidney International Reports2468-02492019-08-014811431151Genetic Predisposition for Renal Dysfunction and Incidence of CKD in the Malmö Diet and Cancer StudyChristina-Alexandra Schulz0Gunnar Engström1Anders Christensson2Peter M. Nilsson3Olle Melander4Marju Orho-Melander5Department of Clinical Sciences, Lund University, Malmö, SwedenDepartment of Clinical Sciences, Lund University, Malmö, SwedenDepartment of Nephrology, Lund University, Malmo, SwedenDepartment of Clinical Sciences, Lund University, Malmö, SwedenDepartment of Clinical Sciences, Lund University, Malmö, SwedenDepartment of Clinical Sciences, Lund University, Malmö, Sweden; Correspondence: Marju Orho-Melander, Department of Clinical Sciences, Malmö, CRC, Skåne University Hospital, Jan Waldenströms gata 35, SE 205 02 Malmö, Sweden.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. Keywords: CKD, eGFR, GRS, renal functionhttp://www.sciencedirect.com/science/article/pii/S2468024919301846 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Christina-Alexandra Schulz Gunnar Engström Anders Christensson Peter M. Nilsson Olle Melander Marju Orho-Melander |
spellingShingle |
Christina-Alexandra Schulz Gunnar Engström Anders Christensson Peter M. Nilsson Olle Melander Marju Orho-Melander Genetic Predisposition for Renal Dysfunction and Incidence of CKD in the Malmö Diet and Cancer Study Kidney International Reports |
author_facet |
Christina-Alexandra Schulz Gunnar Engström Anders Christensson Peter M. Nilsson Olle Melander Marju Orho-Melander |
author_sort |
Christina-Alexandra Schulz |
title |
Genetic Predisposition for Renal Dysfunction and Incidence of CKD in the Malmö Diet and Cancer Study |
title_short |
Genetic Predisposition for Renal Dysfunction and Incidence of CKD in the Malmö Diet and Cancer Study |
title_full |
Genetic Predisposition for Renal Dysfunction and Incidence of CKD in the Malmö Diet and Cancer Study |
title_fullStr |
Genetic Predisposition for Renal Dysfunction and Incidence of CKD in the Malmö Diet and Cancer Study |
title_full_unstemmed |
Genetic Predisposition for Renal Dysfunction and Incidence of CKD in the Malmö Diet and Cancer Study |
title_sort |
genetic predisposition for renal dysfunction and incidence of ckd in the malmö diet and cancer study |
publisher |
Elsevier |
series |
Kidney International Reports |
issn |
2468-0249 |
publishDate |
2019-08-01 |
description |
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. Keywords: CKD, eGFR, GRS, renal function |
url |
http://www.sciencedirect.com/science/article/pii/S2468024919301846 |
work_keys_str_mv |
AT christinaalexandraschulz geneticpredispositionforrenaldysfunctionandincidenceofckdinthemalmodietandcancerstudy AT gunnarengstrom geneticpredispositionforrenaldysfunctionandincidenceofckdinthemalmodietandcancerstudy AT anderschristensson geneticpredispositionforrenaldysfunctionandincidenceofckdinthemalmodietandcancerstudy AT petermnilsson geneticpredispositionforrenaldysfunctionandincidenceofckdinthemalmodietandcancerstudy AT ollemelander geneticpredispositionforrenaldysfunctionandincidenceofckdinthemalmodietandcancerstudy AT marjuorhomelander geneticpredispositionforrenaldysfunctionandincidenceofckdinthemalmodietandcancerstudy |
_version_ |
1725867050403889152 |