title: Genetic risk score and risk of stage 3 chronic kidney disease.
abstract: BACKGROUND
  We developed a genetic risk score (GRS) and examined whether the GRS may predict incident stage 3 chronic kidney disease (CKD) independent of common clinical risk factors.
  
  
  METHODS
  The present study included 2,698 individuals who attended the 15th (1977 to 1979) and the 24th exams (1995 to 1998) in the Framingham Original cohort or the 6th (1995 to 1998) and the 8th exams (2005 to 2008) in the Framingham Offspring cohort. A weighted GRS was constructed combining 53 single nucleotide polymorphisms (SNPs) associated with lower creatinine-based estimated glomerular filtration rate (eGFR). Stage 3 CKD was defined as eGFR <60 mL/min/1.73 m2, and incident cases were identified at follow-up after excluding prevalent cases at baseline.
  
  
  RESULTS
  A total of 292 incident cases and 2,406 non-cases were identified over, on average, 11 years of follow-up. After adjustment for sex, age, cohort, baseline eGFR, hypertension, diabetes, and dipstick proteinuria, the odds ratio of incident stage 3 CKD was 1.37 (95%CI: 1.02-1.83) per 10 alleles of the GRS (P = 0.04). There was no statistically significant difference between the C-statistic without and with inclusion of the GRS (0.783 and 0.785, respectively; P = 0.39).
  
  
  CONCLUSIONS
  A GRS developed based on 53 SNPs associated with reduced eGFR was prospectively associated with incident stage 3 CKD. However, this score did not substantially improve discrimination of stage 3 CKD beyond the common clinical risk factors.
authors.affiliation: Framingham Heart Study, Framingham, MA, USA.|Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Jiantao
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Biostatistics, Boston University, Boston, MA, USA.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Framingham Heart Study, Framingham, MA, USA.|Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Shih-Jen
authors.initials: SJ
authors.lastname: Hwang
authors.affiliation: Framingham Heart Study, Framingham, MA, USA.|Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Fox
authors.affiliation: Framingham Heart Study, Framingham, MA, USA. audrey.chu@nih.gov.|Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. audrey.chu@nih.gov.
authors.forename: Audrey Y
authors.initials: AY
authors.lastname: Chu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015995:Prevalence; D016016:Proportional Hazards Models; D051436:Renal Insufficiency, Chronic / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D015203:Reproducibility of Results; D018570:Risk Assessment / Q000379:methods; D012680:Sensitivity and Specificity; D014481:United States / Q000453:epidemiology
chemical_list: D005819:Genetic Markers
keywords: Chronic kidney disease; Estimated glomerular filtration rate; Genetic risk score