Association of the 5'-upstream regulatory region of the alpha7 nicotinic acetylcholine receptor subunit gene (CHRNA7) with schizophrenia.

Abstract

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.

• Authors: Sarah H Stephens, Judith Logel, Amanda Barton, Alexis Franks, Jessica Schultz, Margaret Short, Jane Dickenson, Benjamin James, Tasha E Fingerlin, Brandie Wagner, Colin Hodgkinson, Sharon Graw, Randal G Ross, Robert Freedman, Sherry Leonard
• Journal: Schizophrenia research (Schizophr Res) Vol. 109 Issue 1-3 Pg. 102-12 (Apr 2009) ISSN: 0920-9964 [Print] Netherlands
• PMID: 19181484 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Chrna7 protein, human
• Receptors, Nicotinic
• alpha7 Nicotinic Acetylcholine Receptor

Topics

• Black or African American (genetics)
• Case-Control Studies
• Cell Line
• Chromosome Mapping
• Chromosomes, Human, Pair 15 (genetics)
• Family
• Female
• Genetic Predisposition to Disease
• Genome-Wide Association Study
• Genotype
• Humans
• Linkage Disequilibrium
• Male
• Pedigree
• Polymorphism, Single Nucleotide (genetics)
• Receptors, Nicotinic (genetics)
• Regulatory Sequences, Nucleic Acid (genetics)
• Schizophrenia (genetics)
• White People (genetics)
• alpha7 Nicotinic Acetylcholine Receptor