Cheryl Richards edited Etiology.md  about 8 years ago

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The most important genetics news of the year may have been the presentation by Huang and colleagues at the Tourette World Congress in London this June, reporting on a large collaborative study of copy number variants (CNVs) in approximately 2,500 TS cases and 3,500 controls \citep{Huang:London}. They first tested some CNVs previously reported in various neurological and psychiatric illnesses; the most significant confirmation in this sample was of exonic deletions in _NRXN1_, a gene previously implicated in autism and TS \citep*{24578685}. They also searched for new, large CNVs and identified a novel TS locus, _CNTN6_, that was significant at a whole-genome level by permutation testing. This gene and 4 of the 32 next most likely candidates this analysis identified are neural adhesion molecules \citep*{24578685}. _CNTN6_ is a reasonable candidate for etiologically contributing to TS; its expression in the brain varies during development \citep{18046458}, knockout mice show motor deficits \citep{12884264}, and an independent study found a variety of neurological and psychiatric symptoms (including 2 with OCD) in 14 patients identified by _CNTN6_ CNVs \citep{26257835}. On the other hand, fewer than 1% of TS cases in this sample had CNVs in _CNTN6_, so its overall importance in TS remains to be more fully characterized.  A collaborative genetic study (de Leeuw et al., 2015) \cite{26646788}  demonstrated an association of TS with 33 genes related to glycolysis or glutamine metabolism. None of the individual genes would have survived correction for multiple testing and the results were consistent with a combined effect of many genetic variants of small effect. These results narrow the hunt for genes that may contribute to the development of TS and they also suggest a new direction for future electrophysiological, imaging and pharmacological studies. Researchers used data from the Avon Longitudinal Study of Parents and Children to identify maternal psychological risk factors during pregnancy that increase the risk of tic disorders in offspring \citep{Ben_Shlomo_2015}. The Avon Longitudinal Study is an ongoing, prospective, pre-birth cohort study of all children born in Avon, United Kingdom, between April 1, 1991, and December 31, 1992. Maternal questionnaires were administered throughout pregnancy and they completed questionnaires about themselves and their children's development every 6 months from the child's birth to age 7 and then every year thereafter. In the final multivariate model, chronic maternal anxiety, evident both before and after parturition, was associated with TS or chronic tic disorder in their offspring. The authors suggest that this association may reflect shared genetic susceptibility or prenatal exposure.