Autism and Histamine

Rare copy number variants in tourette syndrome disrupt genes in histaminergic pathways and overlap with autism.

http://www.ncbi.nlm.nih.gov/pubmed/22169095

Child Study Center, Yale University School of Medicine, New Haven, Connecticut 06520, USA.

Studies of copy number variation (CNV) have characterized loci and molecular pathways in a range of neuropsychiatric conditions.

We analyzed rare CNVs in Tourette syndrome (TS) to identify novel risk regions and relevant pathways, to evaluate burden of structural variation in cases versus controls, and to assess overlap of identified variations with those in other neuropsychiatric syndromes.

METHODS:

We conducted a case-control study of 460 individuals with TS, including 148 parent-child trios and 1131 controls. CNV analysis was undertaken using 370 K to 1 M probe arrays, and genotyping data were used to match cases and controls for ancestry. CNVs present in < 1% of the population were evaluated.

RESULTS:

While there was no significant increase in the number of de novo or transmitted rare CNVs in cases versus controls, pathway analysis using multiple algorithms showed enrichment of genes within histamine receptor (subtypes 1 and 2) signaling pathways (p = 5.8 × 10(-4) – 1.6 × 10(-2)), as well as axon guidance, cell adhesion, nervous system development, and synaptic structure and function processes.

Genes mapping within rare CNVs in TS showed significant overlap with those previously identified in autism spectrum disorders but not intellectual disability or schizophrenia. Three large, likely pathogenic, de novo events were identified, including one disrupting multiple gamma-aminobutyric acid receptor genes.

CONCLUSIONS:

We identify further evidence supporting recent findings regarding the involvement of histaminergic and gamma-aminobutyric acidergic mechanisms in the etiology of TS and show an overlap of rare CNVs in TS and autism spectrum disorders.

Advertisements
This entry was posted in Autism, Epigenetics, General, Immune System, Inflammation, Neurology, Physiology, Schizophrenia, Treatment and tagged , , , , , , , , , , . Bookmark the permalink.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s