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Modifier Gene Candidates in Charcot-Marie-Tooth Disease Type 1A: A Case-Only Genome-Wide Association Study. Journal of neuromuscular diseases Tao, F., Beecham, G. W., Rebelo, A. P., Blanton, S. H., Moran, J. J., Lopez-Anido, C., Svaren, J., Abreu, L., Rizzo, D., Kirk, C. A., Wu, X., Feely, S., Verhamme, C., Saporta, M. A., Herrmann, D. N., Day, J. W., Sumner, C. J., Lloyd, T. E., Li, J., Yum, S. W., Taroni, F., Baas, F., Choi, B., Pareyson, D., Scherer, S. S., Reilly, M. M., Shy, M. E., Zuchner, S., Inherited Neuropathy Consortium 2019

Abstract

BACKGROUND: Charcot-Marie-Tooth disease type 1A (CMT1A) is caused by a uniform 1.5-Mb duplication on chromosome 17p, which includes the PMP22 gene. Patients often present the classic neuropathy phenotype, but also with high clinical variability.OBJECTIVE: We aimed to identify genetic variants that are potentially associated with specific clinical outcomes in CMT1A.METHODS: We genotyped over 600,000 genomic markers using DNA samples from 971 CMT1A patients and performed a case-only genome-wide association study (GWAS) to identify potential genetic association in a subset of 644 individuals of European ancestry. A total of 14 clinical outcomes were analyzed in this study.RESULTS: The analyses yielded suggestive association signals in four clinical outcomes: difficulty with eating utensils (lead SNP rs4713376, chr6?:?30773314, P?=?9.91*10-7, odds ratio?=?3.288), hearing loss (lead SNP rs7720606, chr5?:?126551732, P?=?2.08*10-7, odds ratio?=?3.439), decreased ability to feel (lead SNP rs17629990, chr4?:?171224046, P?=?1.63*10-7, odds ratio?=?0.336), and CMT neuropathy score (lead SNP rs12137595, chr1?:?4094068, P?=?1.14*10-7, beta?=?3.014).CONCLUSIONS: While the results require validation in future genetic and functional studies, the detected association signals may point to novel genetic modifiers in CMT1A.

View details for PubMedID 30958311