FOXP2 – Genetic link between Autism and Crohn’s Disease ?

A genome-wide association study on a southern European population identifies a new Crohn’s disease susceptibility locus at RBX1-EP300.

Vall d’Hebron Research Institute, Barcelona, Spain.

Genome-wide association studies (GWAS) have identified multiple risk loci for Crohn’s disease (CD). However, the cumulative risk exerted by these loci is low, and the likelihood that additional, as-yet undiscovered loci contribute to the risk of CD is very high. We performed a GWAS on a southern European population to identify new CD risk loci.


We genotyped 620 901 genome markers on 1341 CD patients and 1518 controls from Spain. The top association signals representing new candidate risk loci were subsequently analysed in an independent replication cohort of 1365 CD patients and 1396 controls.


We identified a genome-wide significant association on chromosome 22q13.2 in the intergenic region between the RBX1 and EP300 genes (single nucleotide polymorphism rs4820425, OR 1.27, 95% CI 1.17 to 1.38, p=3.42E-8). We also found suggestive evidence for the association of the IFNGR2 (21q22.11), FOXP2 (7q31), MACROD2 (20p12.1) and AIF1 (6p21.3) loci with CD risk.


In this GWAS performed on a southern European cohort, we have identified a new risk locus for CD between RBX1 and EP300. This study demonstrates that using populations of different ancestry is a useful strategy to identify new risk loci for CD.


FOXP2 – wiki

Forkhead box protein P2 also known as FOXP2 is a protein that in humans is encoded by the FOXP2 gene,[1] located on human chromosome 7 (7q31, at the SPCH1 locus).[2][3] FOXP2 orthologs[4] have also been identified in all mammals for which complete genome data are available. The FOXP2 protein contains a forkhead-box DNA-binding domain, making it a member of the FOX group of transcription factors, involved in regulation of gene expression. In addition to this characteristic forkhead-box domain, the protein contains a polyglutamine tract, a zinc finger and a leucine zipper.

In humans, mutations of FOXP2 cause a severe speech and language disorder.[1][5] Versions of FOXP2 exist in similar forms in distantly related vertebrates; functional studies of the gene in mice[6] and in songbirds[7] indicate that it is important for modulating plasticity of neural circuits.[8] Outside the brain FOXP2 has also been implicated in development of other tissues such as the lung and gut.[9] FOXP2 directly regulates a large number of downstream target genes.[10][11]

One particular target that is directly downregulated by FOXP2 in human neurons is the CNTNAP2 gene, a member of the neurexin family; variants in this target gene have been associated with common forms of language impairment.[12]


Further Reading

Dr. Daniel Geschwind and FOXP2 Research


Singing Mice, Autism and FOXP2

RBX1-EP300 autism

A 10.6 Mb duplication in the q arm of chromosome 22 was observed in an autistic female with mitochondrial disease.

This entry was posted in Autism, co-morbid, Environment, Epigenetics, epilepsy, Genetics, Gut, Immune System, Inflammation, Neurology, Physiology and tagged , , , , , , , , . Bookmark the permalink.

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