Exome array analysis suggests an increased variant burden in families with schizophrenia
MetadataShow full item record
The exome array assays rare-but-recurrent, likely deleterious, exonic variants and represents an intermediary between single nucleotide polymorphism (SNP) arrays and sequencing for genetic association studies. Multiplex families with multiple affected individuals may be enriched for disease-associated variants of this class compared to unrelated populations. We present an exome array study of schizophrenia in 99 multiplex families (n = 341, including 118 cases) from the Western Australian Family Study of Schizophrenia (WAFSS).Compared to 55,726 individuals from the DIAGRAM sample not selected for schizophrenia, overall allele frequency of exome variants was higher in the WAFSS (P . <. 2.2E-16). This was pronounced in variants nominally associated (P . <. 0.05) with schizophrenia.Genes harbouring variants present only in WAFSS cases were enriched (FDR-corrected . P = 0.05) for membership of the 'extracellular matrix (ECM) - receptor interaction' biological pathway, adding to evidence that processes affecting the composition or turnover of ECM may contribute to neuropsychiatric disease.We did not find individual variants significantly associated with schizophrenia, although like previous studies, power to detect associations of small effect size was low. Cases did not exhibit a higher burden of variants compared to their unaffected relatives and the finding of previous exome chip studies of unrelated samples that 'schizophrenia gene-sets' were enriched for case-only variants was not replicated in the WAFSS.The higher frequency of moderately rare, exonic variants in these multiplex families compared to a population-based sample may account for some of their genetic liability to schizophrenia, and adds to evidence for a role of exome array variants from previous studies of unrelated samples.
Showing items related by title, author, creator and subject.
Blangero, J.; Teslovich, T.; Sim, X.; Almeida, M.; Jun, G.; Dyer, T.; Johnson, M.; Peralta, J.; Manning, A.; Wood, A.; Fuchsberger, C.; Kent, J.; Aguilar, D.; Below, J.; Farook, V.; Arya, R.; Fowler, S.; Blackwell, T.; Puppala, S.; Kumar, S.; Glahn, D.; Moses, Eric; Curran, J.; Thameem, F.; Jenkinson, C.; DeFronzo, R.; Lehman, D.; Hanis, C.; Abecasis, G.; Boehnke, M.; Göring, H.; Duggirala, R.; Almasy, L. (2016)© 2016 The Author(s).Background: The Genetic Analysis Workshops (GAW) are a forum for development, testing, and comparison of statistical genetic methods and software. Each contribution to the workshop includes an application ...
Alcohol Use Disorders Identification Test (AUDIT) scores are elevated in antipsychotic-induced hyperprolactinaemiaLawford, B.; Barnes, M.; Connor, J.; Heslop, Karen; Nyst, P.; Young, R. (2012)Hyperprolactinaemia in antipsychotic treated patients with schizophrenia is a consequence of D2 receptor (DRD2) blockade. Alcohol use disorder is commonly comorbid with schizophrenia and low availability of striatal DRD2 ...
Modelling the co-occurence of Streptococcus pneumoniae with other bacterial and viral pathogens in the upper respiratory tractJacoby, P.; Watson, K.; Bowman, J.; Taylor, A.; Riley, T.; Smith, D.; Lehmann, Deborah (2007)Go to ScienceDirect® Home Skip Main Navigation Links Brought to you by: The University of Western Australia Library Login: + Register Athens/Institution Login Not Registered? - User Name: Password: ...