ArticleBiological psychiatry2013
Follow-up of a major psychosis linkage site in 13q13-q14 reveals significant association in both case-control and family samples.
Article in Biological psychiatry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.
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4 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The genetics of early-onset bipolar disorder: A systematic review.Journal of affective disorders · 2015Pooled it
- Polyunphased: an extension to polytomous outcomes of the Unphased package for family-based genetic association analysis.Statistical applications in genetics and molecular biology · 2017Article
- On the validity of within-nuclear-family genetic association analysis in samples of extended families.Statistical applications in genetics and molecular biology · 2015Article
- Extension of the generalized disequilibrium test to polytomous phenotypes and two-locus models.Frontiers in genetics · 2014Article
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8 authors.
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Abstract
backgroundWe previously reported a genome-wide significant linkage for major psychosis in chromosome 13q13-q14.
methodsAn 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.
resultsAn 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)).
conclusionsCase-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.
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