Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton General Hospital, McMaster University, Hamilton, Ontario, Canada.
Departments of Clinical Epidemiology and Biostatistics.
J Clin Psychiatry. 2015 Dec;76(12):e1611-8. doi: 10.4088/JCP.14m09720.
Observational studies have shown a positive association between obesity (body mass index [BMI] ≥ 30 kg/m2) and depression. Around 120 obesity-associated loci have been identified, but genetic variants associated with depression remain elusive. Recently, our team reported that the fat mass and obesity-associated (FTO) gene rs9939609 obesity-risk variant is paradoxically inversely associated with the risk of depression. This finding raises the question as to whether other obesity-associated genetic variants are also associated with depression.
Twenty-one obesity gene variants other than FTO were selected from a custom ∼50,000 single-nucleotide polymorphisms (SNPs) genotyping array (ITMAT-Broad-CARe array). Associations of these 21 SNPs and an unweighted genotype score with BMI and major depressive disorder (determined using the DSM-IV diagnostic criteria) were tested in 3,209 cases and 14,195 noncases, using baseline data collected from July 2001 to August 2003 from the multiethnic EpiDREAM study.
Body mass index was positively associated with depression status (odds ratio [OR] = 1.02; 95% CI, 1.02-1.03 per BMI unit; P = 2.9 × 10(-12), adjusted for age, sex, and ethnicity). Six of 21 genetic variants (rs1514176 [TNN13K], rs2206734 [CDKAL1], rs11671664 [GIPR], rs2984618 [TAL1], rs3824755 [NT5C2], and rs7903146 [TCF7L2]) and the genotype score were significantly associated with BMI (1.47 × 10(-14) ≤ P ≤ .04). Of the 21 SNPs, TAL1 rs2984618 obesity-risk allele was associated with a higher risk of major depressive disorder (P = 1.79 × 10(-4), adjusted for age, sex, BMI, and ethnicity), and BDNF rs1401635 demonstrated significant ethnic-dependent association with major depressive disorder (OR = 0.88; 95% CI, 0.80-0.97; P = .01 in non-Europeans and OR = 1.11; 95% CI, 1.02-1.20; P = .02 in Europeans; Pinteraction = 2.73 × 10(-4)). The genotype score, calculated with or without FTO rs9939609, and adjusted for the same covariates, was not associated with depression status.
Our data support the view that the association between obesity and major depressive disorder at the observational level may be explained, at least in part, by shared genetic factors.
观察性研究表明，肥胖（体重指数[BMI]≥30kg/m2）与抑郁症之间存在正相关关系。已经确定了大约 120 个与肥胖相关的基因座，但与抑郁症相关的遗传变异仍然难以捉摸。最近，我们的团队报告说，脂肪量和肥胖相关（FTO）基因 rs9939609 肥胖风险变异与抑郁症的风险呈反比相关。这一发现提出了一个问题，即其他与肥胖相关的遗传变异是否也与抑郁症有关。
从定制的约 50,000 个单核苷酸多态性（SNP）基因分型阵列（ITMAT-Broad-CARe 阵列）中选择了除 FTO 以外的 21 个肥胖基因变异。使用 2001 年 7 月至 2003 年 8 月从多民族 EpiDREAM 研究中收集的基线数据，在 3209 例病例和 14195 例非病例中，测试了这些 21 个 SNP 和未加权基因型评分与 BMI 和重度抑郁症（使用 DSM-IV 诊断标准确定）之间的关联。
BMI 与抑郁症状态呈正相关（比值比[OR] = 1.02；95%置信区间[CI]，每 BMI 单位 1.02-1.03；P = 2.9×10(-12)，调整年龄、性别和种族）。21 个遗传变异中的 6 个（rs1514176[TNN13K]、rs2206734[CDKAL1]、rs11671664[GIPR]、rs2984618[TAL1]、rs3824755[NT5C2]和 rs7903146[TCF7L2]）和基因型评分与 BMI 显著相关（1.47×10(-14)≤P≤.04）。在 21 个 SNP 中，TAL1 rs2984618 肥胖风险等位基因与重度抑郁症的风险增加相关（P = 1.79×10(-4)，调整年龄、性别、BMI 和种族），BDNF rs1401635 表现出与重度抑郁症的显著种族依赖性关联（OR = 0.88；95%CI，0.80-0.97；P =.01 在非欧洲人群中，OR = 1.11；95%CI，1.02-1.20；P =.02 在欧洲人群中；Pinteraction = 2.73×10(-4)）。使用或不使用 FTO rs9939609 计算的基因型评分，并调整相同的协变量，与抑郁症状态无关。
我们的数据支持这样一种观点，即肥胖与重度抑郁症之间在观察性水平上的关联至少部分可以用共同的遗传因素来解释。
