Linkage disequilibrium for schizophrenia at the chromosome 15q13-14 locus of the alpha7-nicotinic acetylcholine receptor subunit gene (CHRNA7).
The transmission/disequilibrium test was used for fine mapping of the linkage of schizophrenia to the chromosome 15q13-14 region, the site of a candidate gene, the alpha7 nicotinic acetylcholine receptor subunit gene (CHRNA7), in parent-child triads from the NIMH Schizophrenia Genetics Initiative families. This candidate gene was identified from neurobiological studies of deficits in schizophrenics of the inhibitory gating of the P50 auditory evoked potential. The neurobiological deficit was also used as a phenotype for subsequent linkage analysis. In the present study, significant genotype-wise disequilibrium (P < 0.007) was found at D15S165, a polymorphic simple sequence marker physically located within 1 megabase of both CHRNA7 and a partially duplicated, expressed sequence that includes exons 5-10 of CHRNA7. Replication of this result was found in an additional set of families. The results support this region as a chromosomal location involved in the genetic transmission of schizophrenia.
Freedman
R
R
Department of Psychiatry, University of Colorado Health Sciences Center, Denver 80262, USA. Robert.Freeman@UCHSC.edu
Leonard
S
S
Gault
J M
JM
Hopkins
J
J
Cloninger
C R
CR
Kaufmann
C A
CA
Tsuang
M T
MT
Farone
S V
SV
Malaspina
D
D
Svrakic
D M
DM
Sanders
A
A
Gejman
P
P
D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D005819:Genetic Markers; D006801:Humans; D015810:Linkage Disequilibrium; D010375:Pedigree; D011978:Receptors, Nicotinic / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579167:Chrna7 protein, human; D005819:Genetic Markers; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor