Body composition and fat distribution were found to display differential effects on the incidence and mortality of chronic disease. However, it remained unclear whether there is an interaction between lifestyle factors and genetic susceptibility on body composition and fat distribution. This study investigated the associations of lifestyle and genetic factors with body composition and fat distribution among 121,664 women from the UK Biobank cohort study. Women with a favorable lifestyle had lower body mass index (BMI, –7.72% [95% CI: –7.93%, –7.51%]), fat mass index (FMI, –15.70% [95% CI: –16.09%, –15.30%]), fat-free mass index (FFMI, –2.86% [95% CI: –2.98%, –2.74%]), arm fat ratio (AFR, –5.19%, [95% CI: –5.38%, –5.00%]), and trunk fat ratio (TFR, –0.73%, [95% CI: –0.84%, –0.62%]), but higher leg fat ratio (LFR, 2.30% [95% CI: 2.16%, 2.44%]) than those with an unfavorable lifestyle. Significant interactions between lifestyle factors and genetic susceptibility on BMI, FMI, and AFR were observed (Pinteraction < 0.05). Among women with a high genetic susceptibility to body composition or fat distribution, those with a healthy lifestyle still had a lower BMI, FMI, FFMI, AFR, and TFR, and higher LFR (Ptrend < 0.001). Women who adhere to a favorable lifestyle tend to have healthy body composition and fat distribution and this association is consistent across all strata of genetic risk.

We genotyped six SNPs in the genes of p450 family among paranoid schizophrenics and normal controls. All subjects are unrelated Han Chinese. Three showed polymorphic, and no significant differences in allele or genotype frequencies were detected between patients and controls. Thus we obtained no evidence for the involvement of the polymorphisms in paranoid schizophrenia in the population investigated.

Dysfunctions of glutamatergic and GABAergic neurotransmission are two important hypotheses for the pathogenesis of schizophrenia. Thus, genes in the pathway are candidates for schizophrenia susceptibility. Phosphate-activated glutaminase (GLS), glutamine synthetase (GLUL), glutamic acid decarboxylase (GAD), GABA transaminase (ABAT) and succinic semialdehyde dehydrogenase (ALDH5A1) are five primary enzymes in glutamate and GABA synthetic and degradative pathway. In order to investigate the possible involvement of these genes in the development of paranoid schizophrenia, we genotyped 80 paranoid schizophrenics from northern China and 108 matched controls by polymerase chain reaction (PCR) and restriction fragment length polymorphisms (RFLP) methods or directly sequencing of PCR product. Seven SNPs were found to be polymorphic in the population investigated. No significant differences in the genotype distributions or allele frequencies between patients and controls were found. Therefore, we conclude the polymorphisms studied in the five genes do not play major roles in pathogenesis of paranoid schizophrenia in the population investigated.

The possibility of using genetic control strategies to increase disease resistance to infectious diseases relies on the identification of markers to include in the breeding plans. Possible incomplete exposure of mastitis-free (control) animals, however, is a major issue to find relevant markers in genetic association studies for infectious diseases. Usually, designs based on elite dairy sires are used in association studies, but an epidemiological case–control strategy, based on cows repeatedly field-tested could be an alternative for disease traits. To test this hypothesis, genetic association results obtained in the present work from a cohort of Italian Holstein cows tested for mastitis over time were compared with those from a previous genome-wide scan on Italian Holstein sires genotyped with 50k single nucleotide polymorphisms for de-regressed estimated breeding values for somatic cell counts (SCCs) on Bos taurus autosome (BTA6) and BTA14. A total of 1121 cows were selected for the case–control approach (cases=550, controls=571), on a combination of herd level of SCC incidence and of within herd individual level of SCC. The association study was conducted on nine previously identified markers, six on BTA6 and four on BTA14, using the R statistical environment with the ‘qtscore’ function of the GenABEL package, on high/low adjusted linear score as a binomial trait. The results obtained in the cow cohort selected on epidemiological information were in agreement with those obtained from the previous sire genome-wide association study (GWAS). Six out of the nine markers showed significant association, four on BTA14 (rs109146371, rs109234250, rs109421300, rs109162116) and two on BTA6 (rs110527224 and rs42766480). Most importantly, using mastitis as a case study, the current work further validated the alternative use of historical field disease data in case–control designs for genetic analysis of infectious diseases in livestock.

The influence of an immunosuppressive cytokine, interleukin-10 (IL-10), on the outcome of hepatitis C virus (HCV) infection has been increasingly reported recently. A number of polymorphisms appear to control the level of IL-10 production. Among them, −592C/A, −819C/T and −1082G/A in the IL-10 gene are three most studied single nucleotide polymorphisms. To provide a more definitive conclusion about their association with the risk of HCV infection, a meta-analysis was performed by combining and summarizing a total of 17 studies. A biological justification for the choice of genetic model was provided. The results indicated no significant association between these IL-10 polymorphisms and the susceptibility to HCV infection [–592C/A: odds ratio (OR) 0·99, 95% confidence interval (CI) 0·78–1·25; –819C/T: OR 0·90, 95% CI 0·69–1·18; –1082G/A: OR 1·34, 95% CI 0·90–2·00]. However, this analysis did not account for the possible risk modifications by other factors, such as ethnicity and virus persistence. Therefore, the effects of ethnicity and virus persistence were investigated using Bayesian meta-regression and subgroup analysis. Finally, an extended case-control association study was conducted in a Chinese population involving 1140 subjects. Both serum level and genotype data of IL-10 −1082G/A were determined. As a result, a low prevalence of G allele was observed. Significantly higher IL-10 production was observed in HCV patients, especially patients with the GG genotype.

The proprotein convertase subtilisin/kexin type 1 (PCSK1) gene encodes the prohormone convertase 1/3 enzyme that processes prohormones into functional hormones that, in turn, regulate central and peripheral energy metabolism. Mutations in the human PCSK1 gene cause severe monogenic obesity or confer risk of obesity. We herein investigated the porcine PCSK1 gene with the aim of identifying polymorphisms associated with fat deposition and production traits in Italian heavy pigs. By re-sequencing about 5.1 kb of this gene in 21 pigs of different breeds, we discovered 14 polymorphisms that were organized in nine haplotypes, clearly distributed in two clades of putative European and Asian origin. Then we re-mapped this gene on porcine chromosome 2 and analysed its expression in several tissues including gastric oxyntic mucosa of weanling pigs in which PCSK1 processes the pre-pro-ghrelin into ghrelin, which in turn is involved in the control of feed intake and energy metabolism. Association analyses between PCSK1 single-nucleotide polymorphisms (SNPs) and production, carcass and several other traits were conducted on five groups of pigs from three different experimental designs, for a total of 1221 animals. Results indicated that the analysed SNPs were associated (P < 0.01 or P < 0.05) with several traits including backfat thickness and visible intermuscular fat in Italian Duroc (ID) and growth performances in Italian Large White (ILW) and in ILW × Italian Landrace pigs. However, the effects estimated in the ILW were opposite to the effects reported in the ID pigs. Suggestive association (P < 0.10) was observed with muscle cathepsin B activity, opening, if confirmed, potential applications to reduce the excessive softness defect of the green hams that is of particular concern for the processing industry. The results obtained supported the need to further investigate the PCSK1 gene to fully exploit the value of its variability and apply this information in pig breeding programmes.

Autism is a severe neurodevelopmental disorder of early childhood. Genetic factors play an important role in the aetiology of the disorder. In this study, we considered the NRCAM gene as a candidate gene of autism. This gene is expressed in the central nervous system and located in the 7q region, a susceptibility locus of autism. We conducted a case-control study of 18 single nucleotide polymorphisms (SNPs) within the NRCAM gene for possible association with autism in 170 autistic patients and 214 normal controls in a Japanese population. Seven SNPs in the NRCAM gene were significantly associated with autism, among which rs2300045 indicated the most prominent result (p=0.0009 uncorrected, p=0.017 corrected). In haplotype analyses, several individual haplotypes, including a common NRCAM haplotype C-T-T-C-T-T-G-C for rs3763463, rs1859767, rs1034825, rs2300045, rs2300043, rs2300039, rs722519, and rs2216259, showed a significant association after Bonferroni correction (p=0.0035 uncorrected, p=0.028 corrected). These haplotypes were located in the 5′ intron-2 region of the gene. In addition, we also assessed the above mentioned SNPs and haplotypes using the transmission disequilibrium test with 148 trios of autistic families. Haplotype G-T-T-T-T-C-G-C in the same eight SNPs was also associated with autism. In summary, our findings provide evidence for a significant association of NRCAM with autism. Considering the important role of the NRCAM gene in brain development, our results therefore indicated that the NRCAM gene is one of the strong candidate genes for autism.

ABSTRACT

Up to 60% of OCD patients do not respond to a regular serotonin reuptake inhibitor (SRI) treatment. The purpose of the present study was to determine whether polymorphisms of the serotonin transporter (5-HTT), 5-HT1Dβ, and 5-HT2A receptor genes affect the efficacy of SRI treatment in OCD. Ninety-one outpatients with primary OCD according to DSM-IV criteria consented to the study were randomly assigned a 12-week, double-blind trial to receive dosages titrated upward to 300 mg/day of venlafaxine, or 60 mg/day of paroxetine. Primary efficacy was assessed by the change from baseline on the Yale-Brown obsessive–compulsive scale (Y-BOCS), and response was defined as a ≥25% reduction on the Y-BOCS. All of the paroxetine treated patients, with the G/G genotype of the 5-HT2A polymorphism were responders (χ2 = 8.66, df = 2, p = 0.013). In the venlafaxine treated patients, the majority of responders carried the S/L genotype of the 5-HTTLPR polymorphism (χ2 = 9.71, df = 2, p = 0.008). The small group of patients who both carried the S/L genotype of the 5-HTTLPR polymorphism and the G/G genotype of the 5-HT2A polymorphism responded all to treatment.

The results of this study suggest that the response in paroxetine and in venlafaxine treated OCD patients is associated with the G/G genotype of the 5-HT2A polymorphism and with the S/L genotype of the 5-HTTLPR polymorphism, respectively.