Candidate gene and genome-wide association studies have not identified common variants, which are reliably associated with depression. The recent identification of obesity predisposing genes that are highly expressed in the brain raises the possibility of their genetic contribution to depression. As variation in the intron 1 of the fat mass- and obesity-associated (FTO) gene contributes to polygenic obesity, we assessed the possibility that FTO gene may contribute to depression in a cross-sectional multi-ethnic sample of 6561 depression cases and 21,932 controls selected from the EpiDREAM, INTERHEART, DeCC (depression case-control study) and Cohorte Lausannoise (CoLaus) studies. Major depression was defined according to DSM IV diagnostic criteria. Association analyses were performed under the additive genetic model. A meta-analysis of the four studies showed a significant inverse association between the obesity risk FTO rs9939609 A variant and depression (odds ratio=0.92 (0.89, 0.97), P=3 × 10(-4)) adjusted for age, sex, ethnicity/population structure and body-mass index (BMI) with no significant between-study heterogeneity (I(2)=0%, P=0.63). The FTO rs9939609 A variant was also associated with increased BMI in the four studies (β 0.30 (0.08, 0.51), P=0.0064) adjusted for age, sex and ethnicity/population structure. In conclusion, we provide the first evidence that the FTO rs9939609 A variant may be associated with a lower risk of depression independently of its effect on BMI. This study highlights the potential importance of obesity predisposing genes on depression.

Recent genome-wide association studies have identified several single-nucleotide polymorphisms (SNPs) that are associated with blood pressure (BP)/hypertension. In this study, we aimed to examine the established associations amongst Chinese children. We genotyped six SNPs (ATP2B1 rs17249754, CSK rs1378942, MTHFR rs1801133, CYP17A1 rs1004467, STK39 rs3754777 and FGF5 rs16998073) in Chinese children (N=3077, age range, 6-18 years). Based on the Chinese age- and sex-specific BP standards, 619 hypertensive cases and 2458 controls with normal BP were identified. Of the six SNPs, only ATP2B1 rs17249754 SNP was significantly associated with the risk of hypertension (allelic odds ratio (OR)=1.25, 95% confidence interval (CI): 1.08-1.44, P=0.003). Although all other SNPs showed a trend towards increasing the BP values and risk of hypertension, there was no statistically significant association after false discovery rate analysis. We calculated the weighted risk score using six SNPs, for systolic BP (SBP), diastolic BP (DBP) and hypertension. Each additional weighted risk score was associated with SBP by 1.18 mm Hg (95% CI=0.62-1.73, P<0.001), but not with the DBP (β=0.28, 95% CI=(-0.15)-0.74), and overall increased the risk of hypertension by 1.19-fold (95% CI=1.04-1.35, P=0.01). The present study confirmed the significant association of ATP2B1 rs17249754 with risk of hypertension among Chinese children, but failed to replicate the association of CSK rs1378942, MTHFR rs1801133, CYP17A1 rs1004467, STK39 rs3754777 and FGF5 rs16998073 with BP/risk of hypertension.

CONTEXT: Recent genome-wide association studies have identified several single-nucleotide polymorphisms (SNPs) that are associated with body mass index (BMI)/obesity. OBJECTIVE: As obesity is an independent risk factor for hypertension, the objective of the study was to investigate the associations of obesity susceptibility loci with blood pressure (BP)/hypertension in a population of Chinese children. DESIGN, SETTING AND PARTICIPANTS: This was a genotype-phenotype association study. Participants included 3077 Chinese children, aged 6-18 years. Based on the Chinese age-and sex-specific BP standards, 619 hypertensive cases and 2458 controls with normal BP were identified. MAIN OUTCOME MEASURES: BP was measured by auscultation using a standard clinical sphygmomanometer. RESULTS: Of the 11 SNPs, only FTO rs9939609 was significantly associated with systolic BP (SBP; P ¼ 0.034) and three SNPs were significantly associated with diastolic BP (DBP; GNPDA2 rs10938397: P ¼ 0.026; FAIM2 rs7138803: P ¼ 0.015; NPC1 rs1805081: P ¼ 0.031) after adjustment for age, sex and hypertension status. In addition, three SNPs were significantly associated with hypertension risk after adjustment for age and sex (FTO rs9939609: odds ratio (OR) ¼ 1.35, 95% confidence interval (CI) 1.12-1.62, P ¼ 0.001; MC4R rs17782313: OR ¼ 1.22, 95% CI 1.06-1.42, P ¼ 0.007; GNPDA2 rs10938397: OR ¼ 1.17, 95% CI 1.02-1.34, P ¼ 0.021). After additional adjustment for BMI, none remained significant. The genetic risk score (GRS), based on three significant SNPs (FTO rs9939609, MC4R rs17782313, GNPDA2 rs10938397), showed a positive association with SBP (P ¼ 5.17 Â 10 À 4 ) and risk of hypertension (OR ¼ 1.22, 95% CI 1.12-1.33, P ¼ 6.07 Â 10 À 6 ). Further adjustment for BMI abolished the positive associations (SBP: P ¼ 0.220; DBP: P ¼ 0.305; hypertension: P ¼ 0.052). Only FTO rs9939609 and GRS were statistically associated with hypertension risk in the age-and sex-adjusted model after correction for multiple testing. CONCLUSIONS:The present study demonstrated that FTO rs9939609 and combined SNPs were significantly associated with risk of hypertension, which seems to be dependent on BMI.

CYP17A1 gene encodes the cytochrome P450 enzyme CYP17A1, a key enzyme involved in steroid metabolism. A single nucleotide polymorphism (SNP) near CYP17A1, rs11191548, showed significant association with hypertension in European adults. However, this association has not been demonstrated in children thus far. Additionally, the role of CYP17A1 in elevating blood pressure (BP) is unclear. We investigated the association of rs11191548 with hypertension in Chinese children. A total of 3422 children participated in the study, including 1009 children with elevated BP (EBP, including prehypertension and hypertension) and 2413 children with normal BP. SNP rs11191548 was associated with systolic BP (SBP) (CC vs TT: P ¼ 4.8 Â 10 28--0.77, P ¼ 0.003) in girls, but there was no statistically significant association between the SNP and diastolic BP in boys or girls. Our results also showed that rs11191548 was more significantly associated with SBP and EBP in obese girls than in girls of normal weight. Our study indicated that the SNP rs11191548, near CYP17A1, was associated with EBP in children. Moreover, we found a sex-specific effect of rs11191548 on SBP in Chinese children. Further studies are necessary to clarify the association between this CYP17A1 polymorphism and BP.

Number of teeth lost, mitochondrial SNPs, and haplogroup Y were correlated with cognitive function in this study population.