The Influence of Known Genetic Variants on Subclinical Cardiovascular Outcomes in Childhood: Generation R Study.
BACKGROUND
Genome-wide association studies have identified single-nucleotide polymorphisms (SNPs) for subclinical cardiovascular outcomes in adults. We examined the influence of these variants on the same outcomes in childhood.


RESULTS
In a population-based prospective cohort study among 4137 children, we examined the associations of SNPs, individually and incorporated in genetic risk scores, which were identified in adults for cardiac (2 SNPs for left ventricular end-diastolic diameter and 5 SNPs for aortic root diameter) and blood pressure outcomes (29 SNPs for systolic and diastolic blood pressure, 22 SNPs for mean arterial pressure, and 10 SNPs for pulse pressure) with the same outcomes in children (median age of 6.0 years [95% range, 4.5-8.7]). Weighted and unweighted risk scores for aortic root diameter were associated with childhood aortic root diameter (difference per additional average risk allele 0.09 mm [95% CI: 0.05, 0.13]). Weighted and unweighted risk scores for pulse pressure were associated with childhood pulse pressure (difference per additional average risk allele 0.22 mm Hg [95% CI: 0.08, 0.35] and 0.18 mm Hg [95% CI: 0.05, 0.31], respectively), but not with childhood systolic or diastolic blood pressure or mean arterial pressure. The risk scores for blood pressure and mean arterial pressure were not associated with any of the childhood blood pressure outcomes.


CONCLUSIONS
Genetic risk scores based on SNPs for aortic root diameter and pulse pressure in adults are associated with the same outcomes in children. SNPs related to cardiovascular outcomes in adulthood at least partly influence cardiovascular development from early life onwards.
From the The Generation R Study Group (R.V.G.P., C.M., A.H., V.W.V.J., J.F.F.), Department of Epidemiology (R.V.G.P., C.M., A.H., V.W.V.J., J.F.F.), and Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands (R.V.G.P., C.M., V.W.V.J., J.F.F.).
Rani V G
RV
Punwasi
From the The Generation R Study Group (R.V.G.P., C.M., A.H., V.W.V.J., J.F.F.), Department of Epidemiology (R.V.G.P., C.M., A.H., V.W.V.J., J.F.F.), and Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands (R.V.G.P., C.M., V.W.V.J., J.F.F.).
Claire
C
Monnereau
From the The Generation R Study Group (R.V.G.P., C.M., A.H., V.W.V.J., J.F.F.), Department of Epidemiology (R.V.G.P., C.M., A.H., V.W.V.J., J.F.F.), and Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands (R.V.G.P., C.M., V.W.V.J., J.F.F.).
Albert
A
Hofman
From the The Generation R Study Group (R.V.G.P., C.M., A.H., V.W.V.J., J.F.F.), Department of Epidemiology (R.V.G.P., C.M., A.H., V.W.V.J., J.F.F.), and Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands (R.V.G.P., C.M., V.W.V.J., J.F.F.).
Vincent W V
VW
Jaddoe
From the The Generation R Study Group (R.V.G.P., C.M., A.H., V.W.V.J., J.F.F.), Department of Epidemiology (R.V.G.P., C.M., A.H., V.W.V.J., J.F.F.), and Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands (R.V.G.P., C.M., V.W.V.J., J.F.F.). j.felix@erasmusmc.nl.
Janine F
JF
Felix
D000328:Adult; D001794:Blood Pressure / Q000235:genetics* / Q000502:physiology; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D002319:Cardiovascular System / Q000378:metabolism / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D016014:Linear Models; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D018570:Risk Assessment / Q000379:methods / Q000706:statistics & numerical data; D012307:Risk Factors
blood pressure; cardiovascular diseases; echocardiography