| Abstract |
Observations of impaired glucose regulation inschizophreniaare long-standing, although their pathological and etiological significance is uncertain. One approach to the issue that minimizes environmental variables (e.g., medication and diet) is to determine whether genes related to glucose regulation show genetic linkage toschizophrenia. We examined the potential role of glucose metabolism inschizophreniathrough a genome scan of affection status inschizophreniaand an empirical method for deriving P-values. Data were utilized from the NIMH Genetics Initiative forschizophreniadataset, which comprises a total sample consisting of 71 pedigrees containing 218 nuclear families and 987 individuals. A genome scan with 459 markers spaced at an average of 10 cM intervals was conducted using the linkage analysis program Genehunter separately for European- and African-American groups. Enzymes that regulate glycolysis were identified and the genes regulating these enzymes were located through the Online Mendelian Inheritance in Man (OMIM) website. The focus in this study was on genes located near previously reportedschizophreniasusceptibility regions. The genome-wide significance of these genes toschizophreniawas assessed using permutation testing. When results were adjusted for multiple testing within and across ethnic groups, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 (PFKFB2;染色体1 q32.2)全基因组有实现ance (P = 0.04). In addition, hexokinase 3 (HK3; chromosome 5q35.3) was also suggestive of linkage (P = 0.09). For the European-American sample,PFKFB2(1q32.2), hexokinase 3 (HK3; 5q35.3), and pyruvate kinase 3 (PK3; chromosome 15q23) achieved significance at the 0.05 level. None of the genes showed significance in the African-American sample. Our results provide further support for the view that genes that regulate glucose metabolism may also influence susceptibility toschizophrenia. More generally, they support the view that relationships between glucose dysregulation andschizophreniaare inherent to the disorder, and are not merely epiphenomena related to medication or other treatment factors. |