Genome-Wide Scan for Loci of Adolescent Obesity and Their Relationship with Blood Pressure

Context: 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. Design: This was a genotype-phenotype association study. Setting: The study was conducted in a French-Canadian founder population. Participants: Participants included 598 adolescents, aged 12-18 yr. Intervention: Testing associations between 530,011 single-nucleotide polymorphisms (SNP; Human610W-Quad BeadChip) and obesity measures and between identified SNP and BP. Primary Outcome Measures: 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 x 10(-9)) and MRPS22 (rs7638110, BMI: P = 4.6 x 10(-8)), and the top ones among the latter (P < 5 x 10(-4)) were MC4R (rs17773430, BMI: P = 5.8 x 10(-6)), FTO (rs9930333, BMI: P = 1.9 x 10(-4)), and MTCH2 (rs7120548, BMI: P = 1.9 x 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. (J Clin Endocrinol Metab 97: E145-E150, 2012)