A schizophrenia locus may be located in region 10p15-p11.
In our genomic scan of 265 Irish families with schizophrenia, we have thus far generated modest evidence for the presence of vulnerability genes in three chromosomal regions, i.e., 5q21-q31, 6p24-p22, and 8p22-p21. Outside of those regions, of all markers tested to date, D10S674 produced one of the highest pairwise heterogeneity lod (H-LOD) scores, 3.2 (P = 0.0004), when initially tested on a subset of 88 families. We then tested a total of 12 markers across a region of 32 centimorgans in region 10p15-p11 of all 265 families. The strongest evidence for linkage occurred assuming an intermediate phenotypic definition, and a recessive genetic model. The largest pairwise H-LOD score was found with marker D10S2443 (maximum 1.95, P = 0.005). Using multipoint H-LODs, we found a broad peak (maximum 1.91, P = 0.006) extending over the 11 centimorgans from marker D10S674 to marker D10S1426. Multipoint nonparametric linkage analysis produced a much broader peak, but with the maximum in the same location near D10S2443 (maximum z = 1.88, P = 0.03). Based on estimates from the multipoint analysis, this putative vulnerability locus appears to be segregating in 5-15% of the families studied, but this estimate should be viewed with caution. When evaluated in the context of our genome scan results, the evidence suggests the possibility of a fourth vulnerability locus for schizophrenia in these Irish families, in region 10p15-p11.
Straub
R E
RE
Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Medical College of Virginia/Virginia Commonwealth University, Richmond 23219-1534, USA. rstraub@hsc.vcu.edu
MacLean
C J
CJ
Martin
R B
RB
Ma
Y
Y
Myakishev
M V
MV
Harris-Kerr
C
C
Webb
B T
BT
O'Neill
F A
FA
Walsh
D
D
Kendler
K S
KS
D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D007494:Ireland; D008126:Lod Score; D008297:Male; D010375:Pedigree; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics*
D005819:Genetic Markers