Accumulated common variants in the broader fragile X gene family modulate autistic phenotypes

Autor: Beata Stepniak, Anne Kästner, Giulia Poggi, Marina Mitjans, Martin Begemann, Annette Hartmann, Sandra Van der Auwera, Farahnaz Sananbenesi, Dilja Krueger‐Burg, Gabriela Matuszko, Cornelia Brosi, Georg Homuth, Henry Völzke, Fritz Benseler, Claudia Bagni, Utz Fischer, Alexander Dityatev, Hans‐Jörgen Grabe, Dan Rujescu, Andre Fischer, Hannelore Ehrenreich
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Zdroj: EMBO Molecular Medicine, Vol 7, Iss 12, Pp 1565-1579 (2015)
Druh dokumentu: article
ISSN: 1757-4676
1757-4684
DOI: 10.15252/emmm.201505696
Popis: Abstract Fragile X syndrome (FXS) is mostly caused by a CGG triplet expansion in the fragile X mental retardation 1 gene (FMR1). Up to 60% of affected males fulfill criteria for autism spectrum disorder (ASD), making FXS the most frequent monogenetic cause of syndromic ASD. It is unknown, however, whether normal variants (independent of mutations) in the fragile X gene family (FMR1, FXR1, FXR2) and in FMR2 modulate autistic features. Here, we report an accumulation model of 8 SNPs in these genes, associated with autistic traits in a discovery sample of male patients with schizophrenia (N = 692) and three independent replicate samples: patients with schizophrenia (N = 626), patients with other psychiatric diagnoses (N = 111) and a general population sample (N = 2005). For first mechanistic insight, we contrasted microRNA expression in peripheral blood mononuclear cells of selected extreme group subjects with high‐ versus low‐risk constellation regarding the accumulation model. Thereby, the brain‐expressed miR‐181 species emerged as potential “umbrella regulator”, with several seed matches across the fragile X gene family and FMR2. To conclude, normal variation in these genes contributes to the continuum of autistic phenotypes.
Databáze: Directory of Open Access Journals
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