Biomedical subjects
Nigel Williams
Publications and source records attributed to Nigel Williams.
The heat is on.
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Genomewide linkage scan in schizoaffective disorder: significant evidence for linkage at 1q42 close to DISC1, and suggestive evidence at 22q11 and 19p13.
CONTEXT: Traditionally, the search for genes involved in predisposition to major psychoses has proceeded with separate studies of schizophrenia and bipolar disorder. However, twin data suggest that, in addition to genes with specificity for these phenotypes, there exist genes that simultaneously influence susceptibility to schizophrenia, bipolar disorder, and schizoaffective disorder. OBJECTIVE: To undertake, to our knowledge, the first systematic search for such loci. DESIGN: Genomewide linkage scan. SETTING: Affected individuals were ascertained in the United Kingdom and Ireland from general psychiatric inpatient and outpatient services. PARTICIPANTS: The families were selected for linkage studies of either schizophrenia or bipolar disorder. Pedigrees were selected for the current analysis where there was at least 1 member with DSM-IV schizoaffective disorder, bipolar type. Within these pedigrees, individuals were coded as affected if they had been diagnosed with DSM-IV schizophrenia, schizoaffective disorder of bipolar type, or bipolar I disorder. A total of 24 pedigrees contributed 35 affected sibling pairs to the sample. METHOD: A 10-centimorgan genome scan using microsatellite markers was analyzed using MAPMAKER/SIBS software. RESULTS: A genomewide significant signal (LOD = 3.54) was observed at chromosome 1q42 (near D1S2800), and suggestive LOD scores were observed at chromosomes 22q11 (LOD = 1.96) and 19p13 (LOD = 1.85). No linkage was observed in these regions in our original schizophrenia or bipolar scans in individuals from the United Kingdom. CONCLUSIONS: Our linkage findings strongly support the existence of loci that influence susceptibility across the functional psychosis spectrum. The DISC1 gene lies within 2.5 megabases of our peak marker on chromosome 1q42 and has been previously implicated in schizophrenia, bipolar disorder, and, recently, schizoaffective disorder. Follow-up of this region should use samples enriched for cases of schizoaffective disorder. Our findings have similar implications for the search for genetic variation on chromosome 22q11 that influences susceptibility to psychosis.
Operation of the schizophrenia susceptibility gene, neuregulin 1, across traditional diagnostic boundaries to increase risk for bipolar disorder.
CONTEXT: Family and twin data suggest that, in addition to susceptibility genes specific for bipolar disorder or schizophrenia, genes exist that contribute to susceptibility across the traditional kraepelinian divide. Several studies have provided evidence that variation at the neuregulin 1 (NRG1) gene on chromosome 8p12 influences susceptibility to schizophrenia. The most consistent finding has been that one particular haplotype (the "core" haplotype) is overrepresented in cases compared with control subjects. OBJECTIVE: To investigate the possible role of NRG1 in bipolar disorder. DESIGN: Genetic case-control association analysis. SETTING: Subjects were unrelated and ascertained from general psychiatric inpatient and outpatient services. PARTICIPANTS: Five hundred twenty-nine patients with DSM-IV bipolar I disorder and 1011 controls from the United Kingdom (100% white). METHODS: We genotyped the markers constituting the NRG1 core haplotype in cases and controls and reanalyzed our existing data from 573 DSM-IV schizophrenia cases with this larger set of controls. RESULTS: We found a significant difference in haplotype distribution between bipolar cases and controls globally (P = .003) and specifically for the core haplotype. Frequencies were 10.2% for bipolar cases and 7.8% for controls (effect size, as measured by odds ratio [OR], 1.37; 95% confidence interval [CI], 1.03-1.80; P = .04). The effect size in our bipolar sample was similar to that in our schizophrenia sample (OR, 1.22; 95% CI, 0.92-1.61). In the bipolar cases with predominantly mood-incongruent psychotic features (n = 193), the effect was greater (OR, 1.71; 95% CI, 1.29-2.59; P = .009), as was the case in the subset of schizophrenia cases (n = 27) who had experienced mania (OR, 1.64; 95% CI, 0.54-5.01). CONCLUSIONS: Our findings suggest that neuregulin 1 plays a role in influencing susceptibility to bipolar disorder and schizophrenia and that it may exert a specific effect in the subset of functional psychosis that has manic and mood-incongruent psychotic features.
Streamlined analysis of pooled genotype data in SNP-based association studies.
Several groups have developed methods for estimating allele frequencies in DNA pools as a fast and cheap way for detecting allelic association between genetic markers and disease. To obtain accurate estimates of allele frequencies, a correction factor k for the degree to which measurement of allele-specific products is biased is generally applied. Factor k is usually obtained as the ratio of the two allele-specific signals in samples from heterozygous individuals, a step that can significantly impair throughput and increase cost. We have systematically investigated the properties of k through the use of empirical and simulated data. We show that for the dye terminator primer extension genotyping method we have applied, the correction factor k is substantially influenced by the dye terminators incorporated, but also by the terminal 3' base of the extension primer. We also show that the variation in k is large enough to result in unacceptable error rates if association studies are conducted without regard to k. We show that the impact of ignoring k can be neutralized by applying a correction factor k(max) that can be easily derived, but this at the potential cost of an increase in type I error. Finally, based upon observed distributions for k we derive a method allowing the estimation of the probability pooled data reflects significant differences in the allele frequencies between the subjects comprising the pools. By controlling the error rates in the absence of knowledge of the appropriate SNP-specific correction factors, each approach enhances the performance of DNA pooling, while considerably streamlining the method by reducing time and cost.
Fears grow for amphibians.
Alarm bells have been ringing around the world about the decline in number of many amphibian populations and a new global study deepens concerns about the future of many species. Nigel Williams reports.
UN stalls on human cloning.
The United Nations postponed again a controversial vote on the issue of therapeutic cloning of human stem cells, hampering the widely supported opposition to reproductive cloning but many countries are developing their own legislation.
Reeve's stem-cell legacy.
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The impact of matching the patient's vocabulary: a randomized control trial.
BACKGROUND: Research in general practice emphasizes the importance of matched models, beliefs and vocabulary in the consultation. OBJECTIVE: The present study aimed to explore the impact of matched and unmatched vocabulary on patient satisfaction with consultations. METHODS: The study took place in one inner city general practice. Patients (n=62) were randomized to either matched or unmatched vocabulary consultations when consulting for problems relating to sexual or bodily function or anatomy. Matched consultations required the doctor to use the same vocabulary as the patient. Unmatched consultations required the doctor to use medical vocabulary. Completed questionnaires were received from 60 patients. The main outcome measure was patient satisfaction (using the Medical Interview Satisfaction Scale). This assesses total satisfaction and has four subscales: distress relief; communication comfort; rapport; and compliance intent. Doctor satisfaction with the consultation was also assessed. RESULTS: The results showed that the two groups were comparable for demographic variables and doctor satisfaction. However, patients in the matched consultation group had significantly higher total satisfaction scores and higher ratings of rapport, communication comfort, distress relief and compliance intent than those in the unmatched group. CONCLUSION: The results indicate that a doctor's choice of vocabulary affects patient satisfaction immediately after a general practice consultation and that using the same vocabulary as the patient can improve patient outcomes.
Network plan for genome progress.
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London's global bid.
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Fears grow about animal rights activists.
The British government has blocked entry to a key American animal rights campaigner but there are growing concerns about local developments.
Research costing plans raise fears.
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Pushing the boundaries.
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