Follow-up of a major psychosis linkage site in 13q13-q14 reveals significant association in both case-control and family samples.

TitleFollow-up of a major psychosis linkage site in 13q13-q14 reveals significant association in both case-control and family samples.
Publication TypeJournal Article
Year of Publication2013
AuteursBureau, A, Chagnon, YC, Croteau, J, Fournier, A, Roy, M-A, Paccalet, T, Merette, C, Maziade, M
JournalBiol Psychiatry
Volume74
Issue6
Pagination444-50
Date Published2013 Sep 15
ISSN1873-2402
KeywordsCase-Control Studies, Chromosomes, Human, Pair 13, Family, Female, Genetic Linkage, Humans, Male, Psychotic Disorders, Quebec
Abstract

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.

DOI10.1016/j.biopsych.2013.03.004
Alternate JournalBiol. Psychiatry
PubMed ID23602252
PubMed Central IDPMC4015946
Grant List12854-4 / / Canadian Institutes of Health Research / Canada
74430-2 / / Canadian Institutes of Health Research / Canada
MOP-74430 / / Canadian Institutes of Health Research / Canada
MT-12854 / / Canadian Institutes of Health Research / Canada