Background
We previously reported a genome-wide significant linkage for major psychosis in chromosome
13q13-q14.
Methods
An association analysis was conducted in 247 unrelated DSM-IV schizophrenia (SZ) patients
and 250 unrelated control subjects from the Eastern Quebec population genotyped with
2150 single nucleotide polymorphisms in 13q13-q14. We also used the kindred sample
where linkage was detected (125 SZ, 120 bipolar disorder [BD] and 36 schizoaffective
disorder patients vs. 467 unaffected adult relatives) for replication.
Results
An association of the T allele of rs1156026 found in the case-control sample (odds
ratio [OR] = 1.81, p = 4×10−6, false discovery rate = .01) was replicated in the kindred sample (OR = 1.54, p = .01), strengthening the overall association evidence (p = 8×10−7). The effect size increased in the subset of unrelated patients with a family history
(OR = 2.28) and in the 15 families where SZ was predominant (OR = 2.03). In the kindred
sample, onset of either SZ or BD was, on average, 5 years earlier for T/T compared
with C/C homozygotes, leading to stronger association in patients with onset before
26 years of age (SZ: OR = 2.40, p = 1.3×10−4; SZ, BD, and schizoaffective disorder combined: OR = 1.87, p = 8×10−5).
Conclusions
Case-control and family-based association provided evidence of a locus at 13q13-q14
related to SZ. The proximity of the associated single nucleotide polymorphism with
the linkage signal and the extension of the associated phenotype to major psychosis
with younger age of onset indicate congruence between the linkage and association
signals. The rs1156026 association is novel and factors explaining its nondetection
in previous studies are discussed.
Key Words
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Article info
Publication history
Published online: April 22, 2013
Accepted:
March 6,
2013
Received in revised form:
February 13,
2013
Received:
December 4,
2012
Identification
Copyright
© 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
