1 – Genome-wide scan for genes of adolescent obesity and obesity-related high blood pressure

Hypertension, a typical disorder of middle-aged men, is now beginning to emerge in adolescence. This is mainly because obesity a leading risk factor for hypertension, is becoming more common among children and adolescents. Not all obese individuals develop hypertension, however. This is because genes play a significant role in linking obesity to hypertension. Here, we conducted genome-wide association studies (GWAS) to identify genes of adolescent obesity and obesity-related high blood pressure. The Human610W-Quad Illumina BeadChip, containing >550,000 SNPs, was used to genotype 600 adolescents (age=12-18 years) recruited from a French-Canadian founder population. Body mass index (BMI), body-fat mass and systolic blood pressure (SBP) during a cardiovascular protocol designed to mimic daily-life activities, including changes in posture and mental stress, were analyzed with MERLIN-1.1.2 under an additive model. All variables were adjusted for sex, age and, if appropriate, height. These GWAS identified both novel and wellestablished genes of obesity. The former included PAX5 (rs16933812, p=1.9x10-8) and MRPS22 (rs7638110, p=4.9x10-8) and the latter MC4R (rs17773430, p=5.4x10-6), MTCH2 (rs7120548, p=5.2x10-5) and FTO (rs9930333, p=1.0x10-4). Among these, only PAX5, MRPS22 and FTO were also associated with SBP (p=2.9x10-3, 6.4x10-3 and 3.5x10-3, respectively). In case of these three genes, risk-allele homozygotes compared with non-risk-allele homozygotes showed higher bodyfat mass by 8.1, 3.5 and 3.0 kg, respectively and higher SBP by up to 7.6, 4.1 and 4.4 mmHg, respectively. In summary, GWAS conducted in an adolescent founder population suggest that not all genes increasing the risk for obesity contribute to the elevation of blood pressure.