On the latent structure of problem gambling: a taxometric analysis

Aims To test whether problem gambling is a categorical or dimensional disorder on the basis of two problem gambling assessments. This distinction discriminates between two different conceptualizations of problem gambling: one that problem gambling is defined by its addictive properties, the other that it is a continuum of harm. Method Using The British Gambling Prevalence Survey 2010, a nationally representative sample of the United Kingdom conducted by the National Centre for Social Research, five different taxometric analyses were carried out on cases from two problem gambling screens: the Problem Gambling Severity Index (PGSI) and a measure derived from the DSM‐IV Pathological Gambling criteria. Two further analyses were conducted on the total scores for these measures. Results There was strong evidence that both scales were measuring a categorical construct. Fit indices consistently supported a categorical interpretation [comparison curve fit index (CCFI) > 0.6]. The PGSI analysis indicated the presence of a taxon (CCFIs = 0.633, 0.756). The analysis conducted on the adapted DSM‐IV criteria indicated stronger quantitative support for a taxon (CCFIs = 0.717, 0.811 and 0.756) but items probing a loss of control were inconsistent. The taxometric analyses of both scales support a categorical interpretation (CCFIs = 0.628, 0.567), but extreme caution should be used due to high nuisance covariance. Conclusions Two problem gambling screens (the Problem Gambling Severity Index and a measure derived from the DSM‐IV Pathological Gambling criteria) appear to measure a categorical construct that taps into a categorical, loss of control model of problem gambling. There is some evidence that the two screens measure different aspects of an addiction construct

Genome-wide study identifies association between HLA-B∗55:01 and Self-Reported Penicillin Allergy

Hypersensitivity reactions to drugs are often unpredictable and can be life threatening, underscoring a need for understanding their underlying mechanisms and risk factors. The extent to which germline genetic variation influences the risk of commonly reported drug allergies such as penicillin allergy remains largely unknown. We extracted data from the electronic health records of more than 600,000 participants from the UK, Estonian, and Vanderbilt University Medical Center’s BioVU biobanks to study the role of genetic variation in the occurrence of self-reported penicillin hypersensitivity reactions. We used imputed SNP to HLA typing data from these cohorts to further fine map the human leukocyte antigen (HLA) association and replicated our results in 23andMe’s research cohort involving a total of 1.12 million individuals. Genome-wide meta-analysis of penicillin allergy revealed two loci, including one located in the HLA region on chromosome 6. This signal was further fine-mapped to the HLA-B∗55:01 allele (OR 1.41 95% CI 1.33–1.49, p value 2.04 × 10−31) and confirmed by independent replication in 23andMe’s research cohort (OR 1.30 95% CI 1.25–1.34, p value 1.00 × 10−47). The lead SNP was also associated with lower lymphocyte counts and in silico follow-up suggests a potential effect on T-lymphocytes at HLA-B∗55:01. We also observed a significant hit in PTPN22 and the GWAS results correlated with the genetics of rheumatoid arthritis and psoriasis. We present robust evidence for the role of an allele of the major histocompatibility complex (MHC) I gene HLA-B in the occurrence of penicillin allergy