Keywords: Intellectual Disability; ROH
Authors: I. Gandin1,2, F. Faletra2, M. Carella3, V. Pecile2, G. Ferrero4, E. Belligni4, P. Palumbo3, O. Palumbo3, P. Bosco5, C. Romano5, C. Belcaro1, D. Vozzi2, A. P. d'Adamo1,2; 1University of Trieste, Trieste, Italy, 2IRCCS Burlo Garofolo, Trieste, Italy, 3IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy, 4AO citta' della salute e della scienza, Torino, Italy, 5IRCCS Oasi Maria SS, Troina(EN), Italy.
Abstract: Several recent studies focused on the effect of extended homozygosity on highly complex and polygenic traits where recessive inheritance may play an important role. Since excess of homozygosity might increase the risk for disorders like schizophrenia, Alzheimer disease and autism, we have set out a study to investigate the effect of ROHs on the degree of Intellectual Disability (ID). About 370 unrelated individuals with ID were collected and classified into mild/moderate ID (MM-ID) for IQ ranging from 35-40 to 70-75 and severe/profound ID (SP-ID) for IQ below 35-40. High-density SNP array data were processed with the aim of detecting and analyze ROHs. Since different array platform were used, homozygosity and ROHs mean length were compared in MM-ID vs SP-ID separately in each dataset. Results were then combined for a meta-analysis. Our data revealed an association between the amount of homozygosity and the degree of ID, according to the recent findings on autism (Gamsiz et al., 2013). Accounting for principal components to control population stratification, we tested for ROHs mean length and detected significantly (p < 0.005) longer stretches in SP-ID compared to MM-ID. Weaker association was detected in burden ROH analysis, showing an increase of the percentage of genome covered by ROHs for SP-ID cases. Extent of ROHs seems to contribute to the pathogenesis of ID, suggesting that autosomal recessive variants have a crucial role on the modulation of the severity of ID that still need to be investigated.