Systems genetics identifies a convergent gene network for cognition and neurodevelopmental disease
- PMID: 26691832
- DOI: 10.1038/nn.4205
Systems genetics identifies a convergent gene network for cognition and neurodevelopmental disease
Abstract
Genetic determinants of cognition are poorly characterized, and their relationship to genes that confer risk for neurodevelopmental disease is unclear. Here we performed a systems-level analysis of genome-wide gene expression data to infer gene-regulatory networks conserved across species and brain regions. Two of these networks, M1 and M3, showed replicable enrichment for common genetic variants underlying healthy human cognitive abilities, including memory. Using exome sequence data from 6,871 trios, we found that M3 genes were also enriched for mutations ascertained from patients with neurodevelopmental disease generally, and intellectual disability and epileptic encephalopathy in particular. M3 consists of 150 genes whose expression is tightly developmentally regulated, but which are collectively poorly annotated for known functional pathways. These results illustrate how systems-level analyses can reveal previously unappreciated relationships between neurodevelopmental disease-associated genes in the developed human brain, and provide empirical support for a convergent gene-regulatory network influencing cognition and neurodevelopmental disease.
Comment in
-
Gene coexpression modules in human cognition.Nat Neurosci. 2016 Feb;19(2):173-5. doi: 10.1038/nn.4226. Nat Neurosci. 2016. PMID: 26814582 No abstract available.
Similar articles
-
Gene coexpression modules in human cognition.Nat Neurosci. 2016 Feb;19(2):173-5. doi: 10.1038/nn.4226. Nat Neurosci. 2016. PMID: 26814582 No abstract available.
-
Rare and common epilepsies converge on a shared gene regulatory network providing opportunities for novel antiepileptic drug discovery.Genome Biol. 2016 Dec 13;17(1):245. doi: 10.1186/s13059-016-1097-7. Genome Biol. 2016. PMID: 27955713 Free PMC article.
-
Systems biology and gene networks in neurodevelopmental and neurodegenerative disorders.Nat Rev Genet. 2015 Aug;16(8):441-58. doi: 10.1038/nrg3934. Epub 2015 Jul 7. Nat Rev Genet. 2015. PMID: 26149713 Free PMC article. Review.
-
Network- and attribute-based classifiers can prioritize genes and pathways for autism spectrum disorders and intellectual disability.Am J Med Genet C Semin Med Genet. 2012 May 15;160C(2):130-42. doi: 10.1002/ajmg.c.31330. Epub 2012 Apr 12. Am J Med Genet C Semin Med Genet. 2012. PMID: 22499558 Free PMC article.
-
Operative list of genes associated with autism and neurodevelopmental disorders based on database review.Mol Cell Neurosci. 2021 Jun;113:103623. doi: 10.1016/j.mcn.2021.103623. Epub 2021 Apr 29. Mol Cell Neurosci. 2021. PMID: 33932580 Review.
Cited by
-
Molecular genetic aetiology of general cognitive function is enriched in evolutionarily conserved regions.Transl Psychiatry. 2016 Dec 13;6(12):e980. doi: 10.1038/tp.2016.246. Transl Psychiatry. 2016. PMID: 27959336 Free PMC article.
-
Integrative genomics reveals pathogenic mediator of valproate-induced neurodevelopmental disability.Brain. 2022 Nov 21;145(11):3832-3842. doi: 10.1093/brain/awac296. Brain. 2022. PMID: 36071595 Free PMC article.
-
DOT1L activity affects neural stem cell division mode and reduces differentiation and ASNS expression.EMBO Rep. 2023 Aug 3;24(8):e56233. doi: 10.15252/embr.202256233. Epub 2023 Jun 29. EMBO Rep. 2023. PMID: 37382163 Free PMC article.
-
Brains, complex systems and therapeutic opportunities in epilepsy.Seizure. 2021 Aug;90:155-159. doi: 10.1016/j.seizure.2021.02.001. Epub 2021 Feb 6. Seizure. 2021. PMID: 33582003 Free PMC article.
-
Commonalities in epileptogenic processes from different acute brain insults: Do they translate?Epilepsia. 2018 Jan;59(1):37-66. doi: 10.1111/epi.13965. Epub 2017 Dec 15. Epilepsia. 2018. PMID: 29247482 Free PMC article. Review.
Publication types
MeSH terms
Grants and funding
- MR/K026992/1/MRC_/Medical Research Council/United Kingdom
- MC_U120097112/MRC_/Medical Research Council/United Kingdom
- BB/F019394/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom
- CZD/16/6/CSO_/Chief Scientist Office/United Kingdom
- FS/11/25/28740/BHF_/British Heart Foundation/United Kingdom
- MR/M013111/1/MRC_/Medical Research Council/United Kingdom
- G1001245/MRC_/Medical Research Council/United Kingdom
- CZD/16/6/4/CSO_/Chief Scientist Office/United Kingdom
- MC_PC_U127561128/MRC_/Medical Research Council/United Kingdom
- G0700704/MRC_/Medical Research Council/United Kingdom
- MR/L012561/1/MRC_/Medical Research Council/United Kingdom