Open AccessAccumulated common variants in the broader fragile X gene family modulate autistic phenotypes
Author(s) -
Stepniak Beata,
Kästner Anne,
Poggi Giulia,
Mitjans Marina,
Begemann Martin,
Hartmann Annette,
Van der Auwera Sandra,
Sananbenesi Farahnaz,
KruegerBurg Dilja,
Matuszko Gabriela,
Brosi Cornelia,
Homuth Georg,
Völzke Henry,
Benseler Fritz,
Bagni Claudia,
Fischer Utz,
Dityatev Alexander,
Grabe HansJörgen,
Rujescu Dan,
Fischer Andre,
Ehrenreich Hannelore
Publication year - 2015
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201505696
Subject(s) - phenotype , genetics , gene , biology , fragile x , autism , medicine , psychiatry
Fragile X syndrome ( FXS ) is mostly caused by a CGG triplet expansion in the fragile X mental retardation 1 gene ( FMR 1 ). 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 ( FMR 1, FXR 1, FXR 2 ) and in FMR 2 modulate autistic features. Here, we report an accumulation model of 8 SNP s 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 micro RNA 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 FMR 2 . To conclude, normal variation in these genes contributes to the continuum of autistic phenotypes.