Hukic Dzana S, Ösby Urban, Olsson Eric, Hilding Agneta, Östenson Claes-Göran, Gu Harvest F, Ehrenborg Ewa, Edman Gunnar, Schalling Martin, Lavebratt Catharina, Frisén Louise
Departments of aMolecular Medicine and Surgery, Neurogenetics Unit bNeurobiology, Care Sciences and Society, Centre for Family Medicine cClinical Neuroscience dMolecular Medicine and Surgery, Endocrine and Diabetes Unit eMedicine, Cardiovascular Medicine Unit, Karolinska Institutet fCenter for Molecular Medicine, Karolinska University Hospital Solna gDepartment of Adult Psychiatry, PRIMA Barn och Vuxenpsykiatri AB hChild and Adolescent Psychiatry Research Center, Stockholm, Sweden.
Psychiatr Genet. 2017 Dec;27(6):210-218. doi: 10.1097/YPG.0000000000000181.
We examined whether established metabolic risk genetic variants in the population confer a risk for increased waist circumference in patients with schizophrenia spectrum disorders and also an association with schizophrenia spectrum disorders irrespective of waist circumference.
We analyzed the association in (i) a case-case model in which patients with schizophrenia spectrum disorder with increased waist circumference (≥80 cm for women and ≥94 cm for men) (n=534) were compared with patients with normal waist circumference (<80 cm for women; <94 cm for men) (n=124), and in (ii) a case-control model in which schizophrenia spectrum disorder patients with increased waist circumference or irrespective of waist circumference were compared with population-derived controls (n=494) adjusted for age, sex, fasting glucose, smoking, and family history of diabetes.
Genetic variants in five genes (MIA3, MRAS, P2RX7, CAMKK2, and SMAD3) were associated with increased waist circumference in patients with schizophrenia spectrum disorder (P<0.046). Genetic variants in three other genes (PPARD, MNTR1B, and NOTCH2) were associated with increased waist circumference in patients when compared with control individuals (P<0.037). Genetic variants in the PPARD, MNTR1B, NOTCH2, and HNF1B were nominally associated with schizophrenia spectrum disorder irrespective of waist circumference (P<0.027). No differences in waist circumference between specific psychosis diagnoses were detected.
Increased waist circumference in patients with schizophrenia spectrum disorder may be explained, in part, by increased metabolic risk gene burden, and it indicates a shared genetic susceptibility to metabolic disorder and psychosis per se. Along these lines, common metabolic risk genetic variants confer a risk for increased waist circumference in patients with schizophrenia spectrum disorders.
我们研究了人群中已确定的代谢风险基因变异是否会增加精神分裂症谱系障碍患者的腰围风险，以及是否与精神分裂症谱系障碍存在关联，且不受腰围影响。
我们在以下两种模型中分析了这种关联：（i）病例-病例模型，将腰围增加（女性≥80厘米，男性≥94厘米）的精神分裂症谱系障碍患者（n = 534）与腰围正常（女性<80厘米；男性<94厘米）的患者（n = 124）进行比较；（ii）病例-对照模型，将腰围增加或不受腰围影响的精神分裂症谱系障碍患者与根据年龄、性别、空腹血糖、吸烟和糖尿病家族史进行调整的人群对照（n = 494）进行比较。
五个基因（MIA3、MRAS、P2RX7、CAMKK2和SMAD3）的基因变异与精神分裂症谱系障碍患者腰围增加有关（P<0.046）。与对照个体相比，另外三个基因（PPARD、MNTR1B和NOTCH2）的基因变异与患者腰围增加有关（P<0.037）。PPARD、MNTR1B、NOTCH2和HNF1B的基因变异在名义上与精神分裂症谱系障碍有关，且不受腰围影响（P<0.027）。未检测到特定精神病诊断之间腰围的差异。
精神分裂症谱系障碍患者腰围增加可能部分由代谢风险基因负担增加所解释，这表明对代谢紊乱和精神病本身存在共同的遗传易感性。据此，常见的代谢风险基因变异会增加精神分裂症谱系障碍患者腰围增加的风险。
