Genome-wide scan for loci of adolescent obesity and their relationship with blood pressure.
BACKGROUND
Hypertension, typically considered a disorder of adulthood, is now emerging in adolescence. This is mainly due to the growing prevalence of obesity and the fact that excess body fat increases blood pressure (BP).


OBJECTIVE
The objective of the study was to investigate whether genome-wide identified gene loci of obesity are associated with elevated BP in adolescence.


METHODS
This was a genotype-phenotype association study.


METHODS
The study was conducted in a French-Canadian founder population.


METHODS
Participants included 598 adolescents, aged 12-18 yr.


METHODS
Testing associations between 530,011 single-nucleotide polymorphisms (SNP; Human610W-Quad BeadChip) and obesity measures and between identified SNP and BP.


METHODS
Total fat mass (TFM) was assessed with bioelectrical impedance, and body mass index (BMI) was determined with anthropometry. BP was measured beat by beat during an hour-long protocol.


RESULTS
The genome-wide association studies of TFM and BMI revealed two novel and several previously identified loci of obesity. The former were PAX5 (rs16933812, TFM: P = 9.3 × 10(-9)) and MRPS22 (rs7638110, BMI: P = 4.6 × 10(-8)), and the top ones among the latter (P < 5 × 10(-4)) were MC4R (rs17773430, BMI: P = 5.8 × 10(-6)), FTO (rs9930333, BMI: P = 1.9 × 10(-4)), and MTCH2 (rs7120548, BMI: P = 1.9 × 10(-4)). From these five, only the PAX5, MRPS22, and FTO were also associated with BP; their minor allele homozygotes vs. major allele homozygotes showed greater TFM by 2.9-8.0 kg and higher BP by 3.3-6.7 mm Hg.


CONCLUSIONS
Genome-wide association studies conducted in an adolescent founder population revealed two new and a number of previously identified loci of obesity and demonstrated that several but not all of these loci are also associated with elevated BP. These results begin to reveal the genetic architecture of obesity-induced hypertension.
The Hospital for Sick Children, Toronto, Canada.
Melkaye G
MG
Melka
Manon
M
Bernard
Amel
A
Mahboubi
Michal
M
Abrahamowicz
Andrew D
AD
Paterson
Catriona
C
Syme
Anbarasu
A
Lourdusamy
Gunter
G
Schumann
Gabriel T
GT
Leonard
Michel
M
Perron
Louis
L
Richer
Suzanne
S
Veillette
Daniel
D
Gaudet
Tomas
T
Paus
Zdenka
Z
Pausova
D000293:Adolescent; D017668:Age of Onset; D001794:Blood Pressure / Q000235:genetics* / Q000502:physiology; D015992:Body Mass Index; D002170:Canada / Q000453:epidemiology; D002648:Child; D002874:Chromosome Mapping; D005260:Female; D056426:Genetic Loci / Q000235:genetics / Q000502:physiology; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000235:genetics; D008297:Male; D009765:Obesity / Q000150:complications / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D011792:Quebec / Q000453:epidemiology; D054928:Validation Studies as Topic