Impact of the diagnosis definition on linkage detection.
Previous genome scan linkage analyses of the disease Kofendrerd Personality Disorder (KPD) with microsatellites led to detect some regions on chromosomes 1, 3, 5, and 9 that were identical for the three populations AI, KA, and DA but with large differences in significance levels. These differences in results may be explained by the different diagnosis definitions depending on the presence/absence of 12 traits that were used in the 3 populations AI, KA, and DA. Heterogeneity of linkage was thus investigated here according to the absence/presence of each of the 12 traits in the 3 populations. For this purpose, two methods, the triangle test statistic and the predivided sample test were applied to search for genetic heterogeneity. Three regions with a strong heterogeneity of linkage were detected: the region on chromosome 1 according to the presence/absence of the traits a and b, the region on chromosome 3 for the trait b, and the region on chromosome 9 for the traits k and l. These 3 regions were the same as those detected by linkage analyses. No novel region was detected by the heterogeneity tests. Concerning chromosome 1, linkage analyses showed a much stronger evidence of linkage for traits a and b and for a combination of these traits than for KPD. Moreover, there was no indication of linkage to any of the other traits used to define the diagnosis of KPD. A genetic factor located on the chromosome 1 may have been detected here which would be involved specifically in traits a and b or in a combination of these traits.
Dizier
Marie-Hélène
MH
Hôpital Paul Brousse, Bâtiment Leriche, B.P. 1000, 94817 Villejuif Cedex, France. dizier@vjf.inserm.fr
Génin
Emmanuelle
E
Babron
Marie Claude
MC
Bourgain
Catherine
C
D002878:Chromosomes, Human, Pair 1; D030541:Databases, Genetic; D018740:Genetic Heterogeneity; D008040:Genetic Linkage; D005819:Genetic Markers; D005828:Genetics, Population; D006801:Humans; D016013:Likelihood Functions; D010554:Personality Disorders / Q000235:genetics*
D005819:Genetic Markers