Wellcome Trust Centre for Human Genetics

About: Wellcome Trust Centre for Human Genetics is a facility organization based out in Oxford, United Kingdom. It is known for research contribution in the topics: Population & Genome-wide association study. The organization has 2122 authors who have published 4269 publications receiving 433899 citations.

The Genomics and Genetics of Human Infectious Disease Susceptibility

Abstract: A genetic basis for interindividual variation in susceptibility to human infectious diseases has been indicated by twin, adoptee, pedigree, and candidate gene studies. This has led to the identification of a small number of strong genetic associations with common variants for malaria, HIV infection, and infectious prion diseases. Numerous other genes have shown less strong associations with these and some other infectious diseases, such as tuberculosis, leprosy, and persistent hepatitis viral infections. Many immunogenetic loci influence susceptibility to several infectious pathogens. Recent genetic linkage analyses of measures of infection as well as of infectious disease, including some genome-wide scans, have found convincing evidence of genetic linkage to chromosomal regions wherein susceptibility genes have yet to be identified. These studies indicate a highly polygenic basis for susceptibility to many common infectious diseases, with some emerging examples of interaction between variants of specific polymorphic host and pathogen genes.

Severe Malarial Anemia and Cerebral Malaria Are Associated with Different Tumor Necrosis Factor Promoter Alleles

Abstract: Experimental evidence implicates tumor necrosis factor (TNF) in the pathogenesis of malarial anemia, but there are few data relating to this hypothesis. This study found that severely anemic children with Plasmodium falciparum infection have low plasma TNF levels, in contrast to the high levels found in cerebral malaria. A previous case-control study in The Gambia found cerebral malaria, but not severe malarial anemia, was associated with the TNF-308 A allele. This study found that in the same population, severe malarial anemia was associated with the TNF-238 A allele, with an odds ratio of 2.5 (P<.001) after stratification for HLA type. These findings suggest that severe malarial anemia and cerebral malaria are influenced by separate genetic factors situated near the TNF gene.

A118G Single Nucleotide Polymorphism of Human μ-Opioid Receptor Gene Influences Pain Perception and Patient-controlled Intravenous Morphine Consumption after Intrathecal Morphine for Postcesarean Analgesia

Abstract: Background Previous studies have shown that genetic variability at position 118 of the human mu-opioid receptor gene altered patients' response to intravenous morphine. The purpose of this study was to investigate whether this polymorphism contributes to the variability in response to morphine for postcesarean analgesia. Methods After investigators obtained informed consent, 588 healthy women received 0.1 mg intrathecal morphine for postcesarean analgesia. Their blood samples were genotyped for the A118G polymorphism-A118 homozygous (AA), heterozygous (AG), or homozygous for the G allele (GG). Pain scores, the severity of nausea and vomiting, the incidence of pruritus, and the total self-administered intravenous morphine were recorded for the first 24 postoperative hours. Results Two hundred seventy women (46%) were AA, 234 (40%) were AG, and 82 (14%) were GG. The 24-h self-administered intravenous morphine consumption was lowest in the AA group (P = 0.001; mean, 5.9; 95% confidence interval, 5.1-6.8) versus the AG (8.0; 6.9-9.1) and GG groups (9.4; 7.3-11.5). Pain scores were lowest in the AA group and highest in the GG group, with a statistically significant difference detected between AA, AG, and GG (P = 0.049). Total morphine consumption was also influenced by patients' age and paying status. AA group was associated with the highest incidence of nausea (26 of 272 [9.6%]; P = 0.02) versus the other two groups (13 of 234 [5.6%] and 1 of 82 [1.2%] for AG and GG, respectively). Conclusion Genetic variation at position 118 of the mu-opioid receptor is associated with interindividual differences in pain scores, self-administered intravenous morphine, and the incidence of nausea postoperatively.

Association of the DRD2 gene Taq1A polymorphism and alcoholism: a meta-analysis of case-control studies and evidence of publication bias.

Abstract: We investigated the association of the dopamine D2 receptor (DRD2) Taq1A polymorphism and alcoholism, using meta-analytic techniques, and specifically undertook an investigation of possible publication bias. Potential publication bias represents a genuine risk to the integrity of published research, but its impact has rarely been documented. We observed a small effect of the DRD2 Taq1A polymorphism on risk of alcoholism, indicating increased alcoholism in individuals possessing the A1 allele of the Taq1A polymorphism (OR=1.21, 95% CI 1.13-1.30, P<0.001). This association remained significant when data from samples of European and East Asian ancestry were analyzed separately. We did not find evidence for association in high-severity alcoholism compared to low-severity alcoholism. Removing the first published study significantly reduced the magnitude of the pooled effect size estimate, although the association remained significant. In addition, we observed evidence for possible publication bias and for the strength of individual study effect size to be inversely related to year of publication. These results support the association of the DRD2 Taq1A polymorphism with alcoholism. This conclusion is qualified by the possibility of publication bias in the literature and the observed between-study heterogeneity, which indicates that the observed association may differ in strength between populations or may not exist at all in some populations.