Do multiple data sets provide support for a bipolar illness susceptibility locus on chromosome 18?
We carried out nonparametric linkage (NPL) analysis of the five chromosome 18 data sets for bipolar illness, as well as of the combined data set. Prior to analysis, we constructed a common genetic map and computed separate marker allele frequencies for each data set. We also attempted to create two consistent diagnostic categories, Narrow (bipolar I, BPI, only) and Broad. The results of the analysis of the combined data set provided stronger evidence of linkage under the Broad category, but at a level of significance that would be expected to occur by chance 4-5 times in a whole-genome scan. When the data sets were analyzed individually, the NIMH data set showed suggestive evidence of linkage (p = 0.0007). The other four data sets, considered together or separately, failed to support this finding, showing only slightly elevated allele sharing among affecteds at a level that would not be unexpected in an unlinked chromosomal region.
Daly
M
M
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02139, USA.
Kirby
A
A
Kruglyak
L
L
D001714:Bipolar Disorder / Q000175:diagnosis / Q000235:genetics*; D002874:Chromosome Mapping; D002887:Chromosomes, Human, Pair 18; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015233:Models, Statistical; D018709:Statistics, Nonparametric