Association of the 5'-upstream regulatory region of the alpha7 nicotinic acetylcholine receptor subunit gene (CHRNA7) with schizophrenia.
BACKGROUND
The alpha7 neuronal nicotinic acetylcholine receptor subunit gene (CHRNA7) is localized in a chromosomal region (15q14) linked to schizophrenia in multiple independent studies. CHRNA7 was selected as the best candidate gene in the region for a well-documented endophenotype of schizophrenia, the P50 sensory processing deficit, by genetic linkage and biochemical studies.


METHODS
Subjects included Caucasian-Non Hispanic and African-American case-control subjects collected in Denver, and schizophrenic subjects from families in the NIMH Genetics Initiative on Schizophrenia. Thirty-five single nucleotide polymorphisms (SNPs) in the 5'-upstream regulatory region of CHRNA7 were genotyped for association with schizophrenia, and for smoking in schizophrenia.


RESULTS
The rs3087454 SNP, located at position -1831 bp in the upstream regulatory region of CHRNA7, was significantly associated with schizophrenia in the case-control samples after multiple-testing correction (P=0.0009, African American; P=0.013, Caucasian-Non Hispanic); the association was supported in family members. There was nominal association of this SNP with smoking in schizophrenia.


CONCLUSIONS
The data support association of regulatory region polymorphisms in the CHRNA7 gene with schizophrenia.
Stephens
Sarah H
SH
Department of Psychiatry, University of Colorado at Denver, United States.
Logel
Judith
J
Barton
Amanda
A
Franks
Alexis
A
Schultz
Jessica
J
Short
Margaret
M
Dickenson
Jane
J
James
Benjamin
B
Fingerlin
Tasha E
TE
Wagner
Brandie
B
Hodgkinson
Colin
C
Graw
Sharon
S
Ross
Randal G
RG
Freedman
Robert
R
Leonard
Sherry
S
D001741:Black or African American / Q000235:genetics; D016022:Case-Control Studies; D002460:Cell Line; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011978:Receptors, Nicotinic / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*; D044465:White People / Q000235:genetics; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579167:Chrna7 protein, human; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor