Home About us Contact
|
Home About us Contact | ||
|
|
||
Genome-wide Significance (genome-wide + significance)
Selected AbstractsA genome-wide quantitative trait loci scan of neurocognitive performances in families with schizophreniaGENES, BRAIN AND BEHAVIOR, Issue 7 2010Y.-J. Lien Patients with schizophrenia frequently display neurocognitive dysfunction, and genetic studies suggest it to be an endophenotype for schizophrenia. Genetic studies of such traits may thus help elucidate the biological pathways underlying genetic susceptibility to schizophrenia. This study aimed to identify loci influencing neurocognitive performance in schizophrenia. The sample comprised of 1207 affected individuals and 1035 unaffected individuals of Han Chinese ethnicity from 557 sib-pair families co-affected with DSM-IV (Diagnostic and Statistical Manual, Fourth Edition) schizophrenia. Subjects completed a face-to-face semi-structured interview, the continuous performance test (CPT) and the Wisconsin card sorting test (WCST), and were genotyped with 386 microsatellite markers across the genome. A series of autosomal genome-wide multipoint nonparametric quantitative trait loci (QTL) linkage analysis were performed in affected individuals only. Determination of genome-wide empirical significance was performed using 1000 simulated genome scans. One linkage peak attaining genome-wide significance was identified: 12q24.32 for undegraded CPT hit rate [nonparametric linkage z (NPL-Z) scores = 3.32, genome-wide empirical P = 0.03]. This result was higher than the peak linkage signal obtained in the previous genome-wide scan using a dichotomous diagnosis of schizophrenia. The identification of 12q24.32 as a QTL has not been consistently implicated in previous linkage studies on schizophrenia, which suggests that the analysis of endophenotypes provides additional information from what is seen in analyses that rely on diagnoses. This region with linkage to a particular neurocognitive feature may inform functional hypotheses for further genetic studies for schizophrenia. [source] QTL for traits related to humoral immune response estimated from data of a porcine F2 resource populationINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 3 2009K. Wimmers Summary This study aimed to map quantitative trait loci (QTL) for traits related to humoral innate immune defence. Therefore, haemolytic complement activity in the alternative and the classical pathway, serum concentration of C3c and of haptoglobin (HP) were measured in blood samples obtained from F2 piglets (n = 457) of a porcine F2 resource population before and after Mycoplasma hyopneumoniae, Aujeszky's disease virus (Suid herpesvirus I, SuHVI) and porcine reproductive and respiratory syndrome virus (PRRSV) vaccination at 6, 14 and 16 weeks of age. Animals were genotyped at 88 autosomal markers. QTL analysis was performed under the line cross and the half sib. Phenotypic data were adjusted for systematic effects by mixed models with and without repeated measures statement. In total, 46 and 21 estimated QTL positions were detected with genome-wide significance at the 0.05 and 0.01 level, respectively. The proximal region of SSC2 (orthologous to HSA11 0,70 Mb), the distal region of SSC4 (HSA1 95,155 Mb), and the intermediate region of SSC16 (HSA5 0,73 Mb and 150,174 Mb) showed a clustering of estimated QTL positions for complement activity based on the different models. A common genetic background, i.e. a single true QTL, might underlie these QTL positions for related traits. In addition, QTL for antibody titres were detected on SSC1, 2, 6 and 7. With regard to number and magnitude of their impact, QTL for humoral innate immune traits behave like those for other quantitative traits. Discovery of such QTL facilitates the identification of candidate genes for disease resistance and immune competence that are applicable in selective breeding and further research towards improving therapeutic and prophylactic measures. [source] Meta-Analysis of Genome-Wide Scans Provides Evidence for Sex- and Site-Specific Regulation of Bone Mass,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2007John PA Ioannidis Abstract Several genome-wide scans have been performed to detect loci that regulate BMD, but these have yielded inconsistent results, with limited replication of linkage peaks in different studies. In an effort to improve statistical power for detection of these loci, we performed a meta-analysis of genome-wide scans in which spine or hip BMD were studied. Evidence was gained to suggest that several chromosomal loci regulate BMD in a site-specific and sex-specific manner. Introduction: BMD is a heritable trait and an important predictor of osteoporotic fracture risk. Several genome-wide scans have been performed in an attempt to detect loci that regulate BMD, but there has been limited replication of linkage peaks between studies. In an attempt to resolve these inconsistencies, we conducted a collaborative meta-analysis of genome-wide linkage scans in which femoral neck BMD (FN-BMD) or lumbar spine BMD (LS-BMD) had been studied. Materials and Methods: Data were accumulated from nine genome-wide scans involving 11,842 subjects. Data were analyzed separately for LS-BMD and FN-BMD and by sex. For each study, genomic bins of 30 cM were defined and ranked according to the maximum LOD score they contained. While various densitometers were used in different studies, the ranking approach that we used means that the results are not confounded by the fact that different measurement devices were used. Significance for high average rank and heterogeneity was obtained through Monte Carlo testing. Results: For LS-BMD, the quantitative trait locus (QTL) with greatest significance was on chromosome 1p13.3-q23.3 (p = 0.004), but this exhibited high heterogeneity and the effect was specific for women. Other significant LS-BMD QTLs were on chromosomes 12q24.31-qter, 3p25.3-p22.1, 11p12-q13.3, and 1q32-q42.3, including one on 18p11-q12.3 that had not been detected by individual studies. For FN-BMD, the strongest QTL was on chromosome 9q31.1-q33.3 (p = 0.002). Other significant QTLs were identified on chromosomes 17p12-q21.33, 14q13.1-q24.1, 9q21.32-q31.1, and 5q14.3-q23.2. There was no correlation in average ranks of bins between men and women and the loci that regulated BMD in men and women and at different sites were largely distinct. Conclusions: This large-scale meta-analysis provided evidence for replication of several QTLs identified in previous studies and also identified a QTL on chromosome 18p11-q12.3, which had not been detected by individual studies. However, despite the large sample size, none of the individual loci identified reached genome-wide significance. [source] A genome scan for quantitative trait loci affecting three ear traits in a White Duroc × Chinese Erhualian resource populationANIMAL GENETICS, Issue 4 2009J. Ma Summary Chinese Erhualian pigs have larger and floppier ears compared with White Duroc pigs (small, half- or fully-pricked ears). To identify quantitative trait loci (QTL) for ear weight and area as well as erectness, a genome-wide scan with 194 microsatellites was performed in a White Duroc × Chinese Erhualian resource population (>1000 F2 animals). Twenty-three genome-wide significant QTL and 12 suggestive QTL were identified. All QTL for ear erectness and size detected in two previous studies, bar two on SSC6 and 9, were confirmed here. The 1% genome-wide significant QTL at 70 cM on SSC5 and at 58 cM on SSC7 have profound and pleiotropic effects on the three ear traits, with Erhualian alleles increasing weight and area but decreasing erectness. Notably, the 95% confidence interval of the QTL for weight and area on SSC7 spanned only 3 cM. New QTL reaching 1% genome-wide significance were found on SSC8 (at 37 cM) for all three ear traits, on SSC4 and 16 for weight and area, and on SSCX for area. Unexpectedly, Erhualian alleles at these loci were associated with lighter and smaller or erect ear. Some new suggestive QTL were also found on other chromosome regions. Almost all the QTL for weight and area had essentially additive effects, while the QTL for erectness on SSC2, 5 and 7 showed not only additive effects but also partial dominance effects of Erhualian alleles. The two most significant QTL on SSC7 and SSC5 could be promising targets for fine mapping and identification of the causative mutations. [source] | |||||||||||||