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Multiple genes in the 15q13-q14 chromosomal region are associated with schizophrenia

Stephens, Sarah H.a; Franks, Alexisa; Berger, Ralpha; Palionyte, Mildaa; Fingerlin, Tasha E.b; Wagner, Brandieb; Logel, Juditha; Olincy, Anna; Ross, Randal G.a; Freedman, Roberta,c; Leonard, Sherrya,c

doi: 10.1097/YPG.0b013e32834c0c33
Original Articles

Objective: The chromosomal region, 15q13-q14, including the α7 nicotinic acetylcholine receptor gene, CHRNA7, is a replicated region for schizophrenia. This study fine-mapped genes at 15q13-q14 to determine whether the association is unique to CHRNA7.

Methods: Family-based and case–control association studies were performed on Caucasian-non-Hispanic and African-American individuals from 120 families as well as 468 individual patients with schizophrenia and 144 well-characterized controls. Single-nucleotide polymorphism (SNP) markers were genotyped, and association analyses carried out for the outcomes of schizophrenia, smoking, and smoking in schizophrenia.

Results: Three genes were associated with schizophrenia in both ethnic populations: TRPM1, KLF13, and RYR3. Two SNPs in CHRNA7 were associated with schizophrenia in African-Americans, and a second SNP in CHRNA7 was significant for an association with smoking and smoking in schizophrenia in Caucasians.

Conclusion: Results of these studies support association of the 15q13-q14 region with schizophrenia. The broad positive association suggests that more than one 15q gene may be contributing to the disorder, either in combination or through a regulatory mechanism.

aDepartments of Psychiatry

bPreventive Medicine and Biometrics, University of Colorado Denver

cVeterans Affairs Medical Research Center, Denver, Colorado, USA

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Correspondence to Sherry Leonard, PhD, Department of Psychiatry, University of Colorado at Denver, Mailstop 8344, P.O. Box 6511, Aurora, CO 80045, USA Tel: +1 303 724 4426; fax: +1 303 724 4425; e-mail: Sherry.Leonard@ucdenver.edu

Received September 3, 2010

Accepted July 14, 2011

© 2012 Lippincott Williams & Wilkins, Inc.