Ilija Kovac | PubMed Health

PubMed2003

Importance sampling method of correction for multiple testing in affected sib-pair linkage analysis.

Using the Genetic Analysis Workshop 13 simulated data set, we compared the technique of importance sampling to several other methods designed to adjust p-values for multiple testing: the Bonferroni correction, the method proposed by Feingold et al., and naïve Monte Carlo simulation. We performed affected sib-pair linkage analysis for each of the 100 replicates for each of five binary traits and adjusted the derived p-values using each of the correction methods. The type I error rates for each correction method and the ability of each of the methods to detect loci known to influence trait values were compared. All of the methods considered were conservative with respect to type I error, especially the Bonferroni method. The ability of these methods to detect trait loci was also low. However, this may be partially due to a limitation inherent in our binary trait definitions.

Computer Simulation↗

PubMed2002

Evidence in an international sample of alcohol-dependent subjects of subgroups with specific symptom patterns of antisocial personality disorder.

BACKGROUND: An earlier latent class analysis (LCA) of the symptoms of antisocial personality disorder in alcohol-dependent subjects enrolled in the Montreal sample of the WHO/ISBRA Study on State and Trait Markers of Alcohol Use and Dependence suggested a three-class qualitative solution. The present analysis of a larger, international WHO/ISBRA sample provides evidence of a four-class solution with expanded symptomatic differentiation. METHODS: An unrestricted LCA of 15 antisocial behaviors expressed after 15 years of age was performed in 465 males with DSM-IV diagnosis of alcohol dependence, from the Montreal center (n = 120, overlapping the previous LCA), Helsinki (n = 80), São Paolo (n = 145), Sapporo (n = 22), and Sydney (n = 98); subjects were of various races, were ascertained from various sources, and showed a wide range of social adjustment. RESULTS: Four latent classes that appeared to differ qualitatively were identified. For descriptive purposes, the classes are termed socially adjusted adults (SAA, n = 197), antisocial work-adjusted adults (AWAA, n = 126), antisocial work-maladjusted adults (AWMA, n = 120), and antisocial aggressive adults (AAA, n = 23). The AAA class had the earliest age of onset for alcohol dependence, which decreased across classes. Proportion of alcohol-dependent first-degree relatives was low in the SAA class (13.6%), moderate in the AWAA and the AWMA classes (20.8% and 18.7% respectively), and high in the AAA class (33.3%). CONCLUSIONS: It is unknown if and to what extent racial, cultural, and ascertainment heterogeneity between collaborating centers might have influenced these analyses. The results presented here show qualitative differences among antisocial alcohol-dependent individuals in job adjustment and aggressive behavior, but only the latter distinction was relevant to familial alcohol dependence. Moreover, both the aggressive class and socially adjusted class differed in familial loading for alcohol dependence from the remaining two antisocial classes. These data provide improved empirical support for qualitative differentiation of aggressive from nonaggressive antisocial alcohol-dependent individuals and might also have nosological implications for antisocial personality disorder.

Adolescent↗