The Gene-Environment Interaction Study Of Overweight/obesity In The Chinese Han Adolescent And The Association Study Between GRIK4 Polymorphisms And Severe Mental Illness In Chinese Han Population

Obesity is a complex health problem commonly caused by a combination of excessive food intake,lack of physical activity,and genetic susceptibility15,31.In 2015,about 603 million adults and 107 million children were obese all over the world1,9.Moreover,health issues related to obesity are also linked with decreased life expectancy and increased economic burden.Nowadays,Obesity has become a global health problem and affected individuals in both the developing and developed worlds.Being overweight/obesity during childhood and adolescence increases the risk of diabetes hypertension,cardiovascular diseases,type 2 diabetes and certain types of cancer23.According to the long-term consequences,overweight adolescents have a 70 percent chance of becoming overweight or obese adults,and this chance commonly increases to 80 percent if one or more parent is overweight or obese20,25.Despite plenty of discoveries concerning the cause of the current global obesity,little is known about the pathogenesis of obesity,and few effective therapies exist.Psychiatric disorders are affected by biology factors,psychological factors and environmental factors,and characterized by abnormal feels,thinks,perceives or behaviors.Psychiatric disorders are public health problems,accounting for 13% of the global burden of disease.The first part of this thesis is focus on the Gene-Environment interaction study of overweight/obesity.We chose 18 SNPs from 9 genes(OLFM4,HOXB5,LEPR,UCP1,PPARD,FTO,MC4 R,UCP2,INSIG2)and we recruited 400 subjects including 222 controls and 178 overweight/obesity adolescents.For each subjects,peripheral blood was collected and used to SNPs analysis.The environment factors was investigated by questionnaire.We found both the allele frequency and the genotype frequency were significantly different of LEPR gene rs8179183 between controls and overweight/obesity groups.And the C allele mutation was a risk allele in the occurrence of overweight/obesity.We also found rs8179183 was associated with the increase of triglyceride.Moreover,we found the environment were associated with the overweight/obesity,and the interaction between LEPR gene and environment factors played significant role in the occurrence of overweight/obesity in Chinese Han adolescent.In the second part of this thesis,we investigated the association between GIRK4 gene polymorphisms and severe mental illness.Both of schizophrenia(SCZ)and major depressive disorder(MDD)are severe and common psychiatric disorders.And in this thesis,we investigated the association between GRIK4 and schizophrenia and major depressive disorder.The dysfunction of glutamate signal was found to be associated with many psychiatric disorders.We recruited 1034 controls and 1034 schizophrenia patients and 568 MDD patients.We found the GRIK4 rs8179183 in the five chosen SNPS was associated with the MDD.But we did not find the association between GRIK4 and schizophrenia.In this thesis we used case-control study approaches to investigate the overweight/obesity and psychiatric disorders,and we found the genetic factors played important role in the occurrence of overweight/obesity and psychiatric disorders.And these studies might provide some cues for etiology,diagnosis and treatment of overweight/obesity and psychiatric disorders.