Application of Niacin Skin Flush Response in Ordered-Subset Linkage Analysis of Schizophrenia
Date Issued
2009
Date
2009
Author(s)
Huang, Sih-Syuan
Abstract
Objective: Previous studies suggested that the attenuation of flush response to topically applied niacin was specific to patients with schizophrenia, showed familial aggregation in families of patients with schizophrenia, and was more impaired in both patients and non-psychotic relatives from families with higher familial loading for schizophrenia. This study aimed to evaluate the linkage signal for schizophrenia in genome scan by means of ordered subset analysis on the basis of the impaired niacin flush response.ethods: Subjects of this study were part of the participants of the Taiwan Schizophrenia Linkage Study, which collected a nation-wide family sample with at least two siblings fulfilling the DSM-IV criteria for schizophrenia or schizoaffective disorder, depressive type. The genotyping was conducted by the Center for Inherited Disease Research, with 369 microsatellite markers spaced at an average of 9-cM intervals. Among these families, 190 had at least one member with information on the niacin skin test and were included for this study. The mean niacin flush response score averaged over all the family members with the niacin skin test information was used as the covariate for each family. A series of ordered subset linkage analyses was then conducted to increase the homogeneity of the samples by ranking families according to the mean niacin flush response scores in each family, and generate a new maximum nonparametric linkage Z (NPL-Z) score on each chromosome for each subset of families. The statistical significance for a subset-derived increase in linkage signal was evaluated using permutations to obtain a chromosome-wide p value. Then the genome-wide significance level of the OSA linkage result was evaluated using a two-step correction procedure.esults: Two chromosomal regions were found to have significant increases in NPL-Z score by ranking families in descending order of niacin flush score, including 5q35.2 (NPL-Z = 3.65, an increase of 2.97, empirical p = 0.006) and 15q26 (NPL-Z = 3.08, an increase of 2.11, empirical p = 0.047). Both regions reached genome-wide significance level with a nominal p value of 0.00013 and 0.0011, respectively. Meanwhile, we also obtained a significant increase in linkage signal on chromosome 22q13.1 (NPL = 2.26, an increase of 2.09, empirical p = 0.043) by ranking families in ascending order of niacin flush score, through not reaching genome-wide significance (a nominal p value of 0.012). In contrast, there was little evidence of linkage on these regions in the original genome-wide analyses.onclusions: These results suggest that the flush response to niacin may be a marker of underlying heterogeneity in schizophrenia and potentially useful to demarcate subgroups of the disorder with different susceptibility genes.
Subjects
schizophrenia
niacin flush response
genome-wide analysis
ordered subset analysis
Type
thesis
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