TY - JOUR
T1 - Follow-up of a major psychosis linkage site in 13q13-q14 reveals significant association in both case-control and family samples
AU - Bureau, Alexandre
AU - Chagnon, Yvon C.
AU - Croteau, Jordie
AU - Fournier, Alain
AU - Roy, Marc André
AU - Paccalet, Thomas
AU - Mérette, Chantal
AU - Maziade, Michel
N1 - Funding Information:
This work was funded by the Canadian Institutes of Health research (Grants MT-12854 and MOP-74430) and by a Canada Research Chair (#950-200810) in the genetics of neuropsychiatric disorders of which MM is the Chair. The data management system was funded by the Canada Foundation for Innovation Leaders Opportunity Fund (Grant 27592). AB is supported by a research fellowship from the Fonds de recherche du Québec-Santé.
PY - 2013/9/15
Y1 - 2013/9/15
N2 - 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.
AB - 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.
KW - Age of onset
KW - bipolar disorder
KW - genetics
KW - prior linkage evidence
KW - schizophrenia
KW - single nucleotide polymorphisms
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U2 - 10.1016/j.biopsych.2013.03.004
DO - 10.1016/j.biopsych.2013.03.004
M3 - Article
C2 - 23602252
AN - SCOPUS:84882643816
VL - 74
SP - 444
EP - 450
JO - Biological Psychiatry
JF - Biological Psychiatry
SN - 0006-3223
IS - 6
ER -