Tumor necrosis factor-α (TNF-α) polymorphisms may influence dyslipidemia, but their role remains unclear. This case-control study investigated associations between TNF-α gene polymorphisms (-1031T/C, -863C/A, -857C/T, -308G/A, and -238G/A) and dyslipidemia in 595 participants (162 cases, 433 controls) from the Chaoshan region of China. Anthropometric, biochemical, and genetic data were analyzed using Chi-squared tests and logistic regression, with the false discovery rate (FDR) method applied to correct for multiple comparisons. Results revealed that only the -1031T/C and -863C/A polymorphisms were significantly associated with dyslipidemia. Carriers of the TC+CC genotype for -1031T/C (odds ratio [OR]=0.48, 95% CI: 0.30-0.78, PFDR=0.006) and the CA+AA genotype for -863C/A (OR=0.41, 95% CI: 0.24-0.70, PFDR=0.004) had lower odds of dyslipidemia. Protective effects were observed for the C allele at -1031T/C (OR=0.58, PFDR=0.012) and the A allele at -863C/A (OR=0.47, PFDR=0.004). Stratified analyses showed that these associations were significant in males but not females. Functional annotation linked these TNF-α gene polymorphisms to transcription factors (e.g., HNF-1A, STAT1β) in the adipogenesis pathway. This study reveals genetic associations between TNF-α polymorphisms and dyslipidemia, particularly in males, and provides mechanistic insights into their role in transcriptional regulation.

The aim is to investigate the association between apolipoprotein E (ApoE) and panic disorder (PD). Genotyping 92 PD patients [Diagnostic Statistic Manual IV (DSM IV) criteria] and 174 controls no differences were found between both groups. Variation in the ApoE-gene was not associated with the development of PD.

Dystrobrevin binding protein 1 (DTNBP1), or dysbindin, is thought to be critical in regulating the glutamatergic system. While the dopamine pathway is known to be important in the aetiology of schizophrenia, it seems likely that glutamatergic dysfunction can lead to the development of schizophrenia. DTNBP1 is widely expressed in brain, levels are reduced in brains of schizophrenia patients and a DTNBP1 polymorphism has been associated with reduced brain expression. Despite numerous genetic studies no DTNBP1 polymorphism has been strongly implicated in schizophrenia aetiology. Using a haplotype block-based gene-tagging approach we genotyped 13 SNPs in DTNBP1 to investigate possible associations with DTNBP1 and schizophrenia. Four polymorphisms were found to be significantly associated with schizophrenia. The strongest association was found with an A/C SNP in intron 7 (rs9370822). Homozygotes for the C allele of rs9370822 were more than two and a half times as likely to have schizophrenia compared to controls. The other polymorphisms showed much weaker association and are less likely to be biologically significant. These results suggest that DTNBP1 is a good candidate for schizophrenia risk and rs9370822 is either functionally important or in disequilibrium with a functional SNP, although our observations should be viewed with caution until they are independently replicated.

Type 2 diabetes (T2D) is a chronic disease that disproportionately affects Indigenous Australians. We have previously reported the localization of a novel T2D locus by linkage analysis to chromosome 2q24 in a large admixed Indigenous Australian pedigree (Busfield et al. (2002). American Journal of Human Genetics, 70, 349–357). Here we describe fine mapping of this region in this pedigree, with the identification of SNPs showing strong association with T2D: rs3845724 (diabetes p = 7 × 10−4), rs4668106 (diabetes p = 9 × 10−4) and rs529002 (plasma glucose p = 3 × 10−4). These associations were successfully replicated in an independent collection of Indigenous Australian T2D cases and controls. These SNPs all lie within the gene encoding ceramide synthase 6 (CERS6) and thus may regulate ceramide synthesis.

Recently, Macgregor et al. (2009) demonstrated significant associations of ADH polymorphisms with reactions to alcohol and alcohol consumption measures in an Australian sample. The aim of the present study was to replicate these findings in a Dutch sample. Survey data on alcohol phenotypes came from 1,754 unrelated individuals registered with the Netherlands Twin Register. SNPs in the ADH gene cluster located on chromosome 4q (n = 491) were subdivided in seven gene sets: ADH5, ADH4, ADH6, ADH1A, ADH1B, ADH1C and ADH7. Within these sets associations of SNPs with alcohol consumption measures, age at onset variables, reactions to alcohol and problem drinking liability were examined. Of the original 38 SNPs studied by Macgregor et al. (2009), six SNPs were not available in our dataset, because one of them had a minor allele frequency < .01 (rs1229984) and five could not be imputed. The remaining SNP associations with alcohol phenotypes as identified by Macgregor et al. (2009) were not replicated in the Dutch sample, after correcting for multiple genotype and phenotype testing. Significant associations were found however, for reactions to alcohol with a SNP in ADH5 (rs6827292, p = .001) and a SNP just upstream of ADH5 (rs6819724, p = .0007) that is in strong LD with rs6827292. Furthermore, an association between age at onset of regular alcohol use and a SNP just upstream of ADH7 (rs2654849, p = .003) was observed. No significant associations were found for alcohol consumption and problem drinking liability. Although these findings do not replicate the earlier findings at the SNP level, the results confirm the role of the ADH gene cluster in alcohol phenotypes.