The Genetic Modifiers of Motor OnsetAge (GeM MOA) Website: Genome-wide Association Analysis for Genetic Modifiers of Huntington’s Disease

Article type: Research Article

Authors: Correia, Kevin^{a; 1} | Harold, Denise^{b; 1; 2; 3} | Kim, Kyung-Hee^{a; c} | Holmans, Peter^{b; 3} | Jones, Lesley^{b; 3} | Orth, Michael^{d; 3} | Myers, Richard H.^{e; 3} | Kwak, Seung^{f; 3} | Wheeler, Vanessa C.^{a; c; 3} | MacDonald, Marcy E.^{a; c; g; 3} | Gusella, James F.^{a; g; h; 3} | Lee, Jong-Min^{a; c; g; 3; *}

Affiliations: [a] Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA | [b] Medical Research Council (MRC) Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, UK | [c] Department of Neurology, Harvard Medical School, Boston, MA, USA | [d] Department of Neurology, University of Ulm, Germany | [e] Department of Neurology and Genome Science Institute, Boston University School of Medicine, Boston, MA, USA | [f] CHDI Foundation, Princeton, NJ, USA | [g] Medical and Population Genetics Program, The Broad Institute of M.I.T. and Harvard, Cambridge, MA, USA | [h] Department of Genetics, Harvard Medical School, Boston, MA, USA

Correspondence: [*] Correspondence to: Jong-Min Lee, 185 Cambridge Street, Boston, MA 02114, USA. Tel.: +1 617 643 9714; Fax: +1 617 726 5735; [email protected]

Note: [1] Equal contribution.

Note: [2] Present address: Neuropsychiatric Genetics Research Group, Department of Psychiatry, Institute of Molecular Medicine, Trinity College Dublin, Ireland.

Note: [3] Founding GeM-HD Consortium investigators.

Abstract: Background: Huntington’s disease (HD) is a dominantly inherited disease caused by a CAG expansion mutation in HTT. The age at onset of clinical symptoms is determined primarily by the length of this CAG expansion but is also influenced by other genetic and/or environmental factors. Objective: Recently, through genome-wide association studies (GWAS) aimed at discovering genetic modifiers, we identified loci associated with age at onset of motor signs that are significant at the genome-wide level. However, many additional HD modifiers may exist but may not have achieved statistical significance due to limited power. Methods: In order to disseminate broadly the entire GWAS results and make them available to complement alternative approaches, we have developed the internet website “GeM MOA” where genetic association results can be searched by gene name, SNP ID, or genomic coordinates of a region of interest. Results: Users of the Genetic Modifiers of Motor Onset Age (GeM MOA) site can therefore examine support for association between any gene region and age at onset of HD motor signs. GeM MOA’s interactive interface also allows users to navigate the surrounding region and to obtain association p-values for individual SNPs. Conclusions: Our website conveys a comprehensive view of the genetic landscape of modifiers of HD from the existing GWAS, and will provide the means to evaluate the potential influence of genes of interest on the onset of HD. GeM MOA is freely available at https://www.hdinhd.org/.

DOI: 10.3233/JHD-150169

Journal: Journal of Huntington's Disease, vol. 4, no. 3, pp. 279-284, 2015