Genome-wide profiling of blood pressure in adults and children.
Hypertension is an important determinant of cardiovascular morbidity and mortality and has a substantial heritability, which is likely of polygenic origin. The aim of this study was to assess to what extent multiple common genetic variants contribute to blood pressure regulation in both adults and children and to assess overlap in variants between different age groups, using genome-wide profiling. Single nucleotide polymorphism sets were defined based on a meta-analysis of genome-wide association studies on systolic blood pressure and diastolic blood pressure performed by the Cohort for Heart and Aging Research in Genome Epidemiology (n=29 136), using different P value thresholds for selecting single nucleotide polymorphisms. Subsequently, genetic risk scores for systolic blood pressure and diastolic blood pressure were calculated in an independent adult population (n=2072) and a child population (n=1034). The explained variance of the genetic risk scores was evaluated using linear regression models, including sex, age, and body mass index. Genetic risk scores, including also many nongenome-wide significant single nucleotide polymorphisms, explained more of the variance than scores based only on very significant single nucleotide polymorphisms in adults and children. Genetic risk scores significantly explained ≤1.2% (P=9.6*10(-8)) of the variance in adult systolic blood pressure and 0.8% (P=0.004) in children. For diastolic blood pressure, the variance explained was similar in adults and children (1.7% [P=8.9*10(-10)] and 1.4% [P=3.3*10(-5)], respectively). These findings suggest the presence of many genetic loci with small effects on blood pressure regulation both in adults and children, indicating also a (partly) common polygenic regulation of blood pressure throughout different periods of life.
The Generation R Study Group (Ae-006), Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
Hendrik R
HR
Taal
Germaine C
GC
Verwoert
Ayse
A
Demirkan
A Cecile J W
AC
Janssens
Kenneth
K
Rice
Georg
G
Ehret
Albert V
AV
Smith
Ben F J
BF
Verhaaren
Jacqueline C M
JC
Witteman
Albert
A
Hofman
Meike W
MW
Vernooij
Andre G
AG
Uitterlinden
Fernando
F
Rivadeneira
M Arfan
MA
Ikram
Daniel
D
Levy
Albert J
AJ
van der Heijden
Vincent W V
VW
Jaddoe
Cornelia M
CM
van Duijn
D000375:Aging / Q000235:genetics* / Q000502:physiology; D001794:Blood Pressure / Q000235:genetics* / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D005260:Female; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D020641:Polymorphism, Single Nucleotide / Q000235:genetics / Q000502:physiology; D012307:Risk Factors