Examination of genetic linkage of chromosome 15 to schizophrenia in a large Veterans Affairs Cooperative Study sample.
Previous studies have reported genetic linkage evidence for a schizophrenia gene on chromosome 15q. Here, chromosome 15 was examined by genetic linkage analysis using 166 schizophrenia families, each with two or more affected subjects. The families, assembled from multiple centers by the Department of Veterans Affairs Cooperative Study Program, consisted of 392 sampled affected subjects and 216 affected sibling pairs. By DSM-III-R criteria, 360 subjects (91.8%) had a diagnosis of schizophrenia and 32 (8.2%) were classified as schizo-affective disorder, depressed. Participating families had diverse ethnic backgrounds. The largest single group were northern European American families (n = 62, 37%), but a substantial proportion was African American kindreds (n = 60, 36%). The chromosome 15 markers tested were spaced at intervals of approximately 10 cM over the entire chromosome and 2-5 cM for the region surrounding the alpha-7 nicotinic cholinergic receptor subunit gene (CHRNA7). These markers were genotyped and the data analyzed using semiparametric affecteds-only linkage analysis. In the European American families, there was a maximum Z-score of 1.65 between markers D15S165 and D15S1010. These markers are within 1 cM from CHRNA-7, the site previously implicated in schizophrenia. However, there was no evidence for linkage to this region in the African America kindreds.
Tsuang
D W
DW
Veterans Affairs Puget Sound Health Care System, Mental Illness, Research, Education and Clinical Center, Seattle, Washington 98108, USA.
Skol
A D
AD
Faraone
S V
SV
Bingham
S
S
Young
K A
KA
Prabhudesai
S
S
Haverstock
S L
SL
Mena
F
F
Menon
A S
AS
Bisset
D
D
Pepple
J
J
Sauter
F
F
Baldwin
C
C
Weiss
D
D
Collins
J
J
Boehnke
M
M
Schellenberg
G D
GD
Tsuang
M T
MT
D000328:Adult; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D004247:DNA / Q000235:genetics; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D010375:Pedigree; D011978:Receptors, Nicotinic / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics*; D014728:Veterans; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579167:Chrna7 protein, human; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D004247:DNA