Dataset Information

Meta-analysis of 32 genome-wide linkage studies of schizophrenia.

ABSTRACT: A genome scan meta-analysis (GSMA) was carried out on 32 independent genome-wide linkage scan analyses that included 3255 pedigrees with 7413 genotyped cases affected with schizophrenia (SCZ) or related disorders. The primary GSMA divided the autosomes into 120 bins, rank-ordered the bins within each study according to the most positive linkage result in each bin, summed these ranks (weighted for study size) for each bin across studies and determined the empirical probability of a given summed rank (P(SR)) by simulation. Suggestive evidence for linkage was observed in two single bins, on chromosomes 5q (142-168 Mb) and 2q (103-134 Mb). Genome-wide evidence for linkage was detected on chromosome 2q (119-152 Mb) when bin boundaries were shifted to the middle of the previous bins. The primary analysis met empirical criteria for 'aggregate' genome-wide significance, indicating that some or all of 10 bins are likely to contain loci linked to SCZ, including regions of chromosomes 1, 2q, 3q, 4q, 5q, 8p and 10q. In a secondary analysis of 22 studies of European-ancestry samples, suggestive evidence for linkage was observed on chromosome 8p (16-33 Mb). Although the newer genome-wide association methodology has greater power to detect weak associations to single common DNA sequence variants, linkage analysis can detect diverse genetic effects that segregate in families, including multiple rare variants within one locus or several weakly associated loci in the same region. Therefore, the regions supported by this meta-analysis deserve close attention in future studies.

SUBMITTER: Ng MY

PROVIDER: S-EPMC2715392 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Meta-analysis of 32 genome-wide linkage studies of schizophrenia.

Ng M Y M MY Levinson D F DF Faraone S V SV Suarez B K BK DeLisi L E LE Arinami T T Riley B B Paunio T T Pulver A E AE Irmansyah Holmans P A PA Escamilla M M Wildenauer D B DB Williams N M NM Laurent C C Mowry B J BJ Brzustowicz L M LM Maziade M M Sklar P P Garver D L DL Abecasis G R GR Lerer B B Fallin M D MD Gurling H M D HM Gejman P V PV Lindholm E E Moises H W HW Byerley W W Wijsman E M EM Forabosco P P Tsuang M T MT Hwu H-G HG Okazaki Y Y Kendler K S KS Wormley B B Fanous A A Walsh D D O'Neill F A FA Peltonen L L Nestadt G G Lasseter V K VK Liang K Y KY Papadimitriou G M GM Dikeos D G DG Schwab S G SG Owen M J MJ O'Donovan M C MC Norton N N Hare E E Raventos H H Nicolini H H Albus M M Maier W W Nimgaonkar V L VL Terenius L L Mallet J J Jay M M Godard S S Nertney D D Alexander M M Crowe R R RR Silverman J M JM Bassett A S AS Roy M-A MA Mérette C C Pato C N CN Pato M T MT Roos J Louw JL Kohn Y Y Amann-Zalcenstein D D Kalsi G G McQuillin A A Curtis D D Brynjolfson J J Sigmundsson T T Petursson H H Sanders A R AR Duan J J Jazin E E Myles-Worsley M M Karayiorgou M M Lewis C M CM

Molecular psychiatry 20081230 8

A genome scan meta-analysis (GSMA) was carried out on 32 independent genome-wide linkage scan analyses that included 3255 pedigrees with 7413 genotyped cases affected with schizophrenia (SCZ) or related disorders. The primary GSMA divided the autosomes into 120 bins, rank-ordered the bins within each study according to the most positive linkage result in each bin, summed these ranks (weighted for study size) for each bin across studies and determined the empirical probability of a given summed r ...[more]

PMID: 19349958

Similar Datasets

Project description:Schizophrenia is a chronic and debilitating psychiatric condition affecting slightly more than 1% of the population worldwide and it is a multifactorial disorder with a high degree of heritability (80%) based on family and twin studies. Increasing lines of evidence suggest intermediate phenotypes/endophenotypes are more associated with causes of the disease and are less genetically complex than the broader disease spectrum. Negative symptoms in schizophrenia are attractive intermediate phenotypes based on their clinical and treatment response features. Therefore, our objective was to identify genetic variants underlying the negative symptoms of schizophrenia by analyzing two genome-wide association (GWA) data sets consisting of a total of 1,774 European-American patients and 2,726 controls. Logistic regression analysis of negative symptoms as a binary trait (adjusted for age and sex) was performed using PLINK. For meta-analysis of two datasets, the fixed-effect model in PLINK was applied. Through meta-analysis we identified 25 single nucleotide polymorphisms (SNPs) associated with negative symptoms with p<5×10(-5). Especially we detected five SNPs in the first two genes/loci strongly associated with negative symptoms of schizophrenia (P(meta-analysis)<6.22×10(-6)), which included three SNPs in the BCL9 gene: rs583583 showed the strongest association at a P(meta-analysis) of 6.00×10(-7) and two SNPs in the C9orf5 (the top SNP is rs643410 with a p = 1.29 ×10(-6)). Through meta-analysis, we identified several additional negative symptoms associated genes (ST3GAL1, RNF144, CTNNA3 and ZNF385D). This is the first report of the common variants influencing negative symptoms of schizophrenia. These results provide direct evidence of using of negative symptoms as an intermediate phenotype to dissect the complex genetics of schizophrenia. However, additional studies are warranted to examine the underlying mechanisms of these disease-associated SNPs in these genes.

Dataset Information

Meta-analysis of 32 genome-wide linkage studies of schizophrenia.

Publications

Meta-analysis of 32 genome-wide linkage studies of schizophrenia.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets