Monday, 13 August 2012

No single SNP associated with autism?

A quote to begin this relatively short post:

"Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level."

One of the conclusions reached in this article by Richard Anney and colleagues* (full-text). SNPs (single nucleotide polymorphism(s) are the tiny rearrangements in our genetic code which have all but replaced the older research fashion of one gene - one condition from times gone by. The theory being that these small mutations might offer some assistance with regards to for example, identifying an individuals risk or response to a condition or pharmacotherapy for disease as has been noted in conditions like breast cancer.

SNPs in relation to autism have been discussed previously on this blog as per posts like this one and this one.  The net result so far suggest that such genetic glitches are present in at least some cases of autism, but - and it is rather a large but - SNPs are a rather complicated area of genetic research. As per the Anney paper, consistent individual SNPs across all cases of autism are not yet apparent.

I don't want to make to much of a meal of the Anney results with regards to the modest individual effects noted by the authors. Suffice to say that based on quite a large dataset numbering in the couple of thousands of participants "no genome-wide significant association with specific common variants" was reported.

Where next I hear you ask? Well, it was unlikely that one single SNP would be apparent across the whole of the autism spectrum similar to the findings based on the long and as yet unsuccessful search for the 'autism gene'. Everyone carries their own mutations and in the most part these don't seem to unduly affect day-to-day health and wellbeing bearing in mind important interfering variables like comorbidity - as in, is the SNP/s related to autism or related to other things like learning disability or epilepsy or other more somatic things? The fact that autism is a constellation of symptoms also makes the interpretation of any findings even more problematic.

More likely that more than one SNP is going to be involved in specific 'types' of autism and there is some degree of interaction between them. A fantastic case for looking more at endophenotypes based on symptoms presentation (including regression as per the latest study from Barger and colleagues**) or even based on possible responsiveness to specific interventions. That and/or the possibility that epigenetics and the methylation / acetylation / phosphorylation of DNA, or histones, is likely to be a more fruitful area of research combining both genes and environment as per the recent suggestion by Emily Simonoff***.

To finish, London has bid farewell to the 2012 Olympic flame and so I leave you with a song from the best of British, Paul McCartney / Wings and 'Live and Let Die'. One small note to the closing ceremony organisers: if you are going to play a Kate Bush song to denote something 'British' outside of just a reference to a hill, make sure its Wuthering Heights. Looking forward to the Rio party.

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* Anney R. et al. Individual common variants exert weak effects on risk for Autism Spectrum Disorders. Human Molecular Genetics. July 2012.

** Barger BD. et al. Prevalence and onset of regression within autism spectrum disorders: a meta-analytic review. JADD. Ausgust 2012.

** Simonoff E. Autism spectrum disorder: prevalence and cause may be bound together. British Journal of Psychiatry. 2012; 201: 88-89.

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ResearchBlogging.org Anney R, Klei L, Pinto D, Almeida J, Bacchelli E, Baird G, Bolshakova N, Bölte S, Bolton PF, Bourgeron T, Brennan S, Brian J, Casey J, Conroy J, Correia C, Corsello C, Crawford EL, de Jonge M, Delorme R, Duketis E, Duque F, Estes A, Farrar P, Fernandez BA, Folstein SE, Fombonne E, Gilbert J, Gillberg C, Glessner JT, Green A, Green J, Guter SJ, Heron EA, Holt R, Howe JL, Hughes G, Hus V, Igliozzi R, Jacob S, Kenny GP, Kim C, Kolevzon A, Kustanovich V, Lajonchere CM, Lamb JA, Law-Smith M, Leboyer M, Le Couteur A, Leventhal BL, Liu XQ, Lombard F, Lord C, Lotspeich L, Lund SC, Magalhaes TR, Mantoulan C, McDougle CJ, Melhem NM, Merikangas A, Minshew NJ, Mirza GK, Munson J, Noakes C, Nygren G, Papanikolaou K, Pagnamenta AT, Parrini B, Paton T, Pickles A, Posey DJ, Poustka F, Ragoussis J, Regan R, Roberts W, Roeder K, Roge B, Rutter ML, Schlitt S, Shah N, Sheffield VC, Soorya L, Sousa I, Stoppioni V, Sykes N, Tancredi R, Thompson AP, Thomson S, Tryfon A, Tsiantis J, Van Engeland H, Vincent JB, Volkmar F, Vorstman J, Wallace S, Wing K, Wittemeyer K, Wood S, Zurawiecki D, Zwaigenbaum L, Bailey AJ, Battaglia A, Cantor RM, Coon H, Cuccaro ML, Dawson G, Ennis S, Freitag CM, Geschwind DH, Haines JL, Klauck SM, McMahon WM, Maestrini E, Miller J, Monaco AP, Nelson SF, Nurnberger JI Jr, Oliveira G, Parr JR, Pericak-Vance MA, Piven J, Schellenberg GD, Scherer SW, Vicente AM, Wassink TH, Wijsman EM, Betancur C, Buxbaum JD, Cook EH, Gallagher L, Gill M, Hallmayer J, Paterson AD, Sutcliffe JS, Szatmari P, Vieland VJ, Hakonarson H, & Devlin B (2012). Individual common variants exert weak effects on the risk for autism spectrum disorderspi. Human molecular genetics PMID: 22843504