Shared Biological Pathways and Processes in Patients with Intellectual Disability: A Multicenter Study

Abstract

Background Although the underlying genetic causes of intellectual disability (ID) continue to be rapidly identified, the biological pathways and processes that could be targets for a potential molecular therapy are not yet known. This study aimed to identify ID-related shared pathways and processes utilizing enrichment analyses.

Methods In this multicenter study, causative genes of patients with ID were used as input for Disease Ontology (DO), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes enrichment analysis.

Results Genetic test results of 720 patients from 27 centers were obtained. Patients with chromosomal deletion/duplication, non-ID genes, novel genes, and results with changes in more than one gene were excluded. A total of 558 patients with 341 different causative genes were included in the study. Pathway-based enrichment analysis of the ID-related genes via ClusterProfiler revealed 18 shared pathways, with lysine degradation and nicotine addiction being the most common. The most common of the 25 overrepresented DO terms was ID. The most frequently overrepresented GO biological process, cellular component, and molecular function terms were regulation of membrane potential, ion channel complex, and voltage-gated ion channel activity/voltage-gated channel activity, respectively.

Conclusion Lysine degradation, nicotine addiction, and thyroid hormone signaling pathways are well-suited to be research areas for the discovery of new targeted therapies in ID patients.

Keywords

neurodevelopmental disorder - intellectual disability - pathway analysis - enrichment analysis - KEGG - ontology

Author Contributions

Ç. G. and D. A. were chief investigators of the present study and responsible for organization and coordination besides the conception and design of the work, acquisition, analysis, and interpretation of data, drafting/revising it critically for important intellectual content. All authors participated in the acquisition of data. G. K. played significant roles in figure editing, analyzing and interpreting data, and drafting the manuscript. Y. O. drafted the manuscript. S.H.K. revised the manuscript. All authors contributed to the writing of the final manuscript, and read and approved the final manuscript.

^* Çağatay Günay and Duygu Aykol contributed equally to the study (first co-authors, shared first authorship).

Publication History

Received: 02 November 2022

Accepted: 08 February 2023

Accepted Manuscript online:
14 February 2023

Article published online:
22 March 2023

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