Journal article
Modifier Gene Candidates in Charcot-Marie-Tooth Disease Type 1A: A Case-Only Genome-Wide Association Study
Journal of neuromuscular diseases, Vol.6(2), pp.201-211
2019
DOI: 10.3233/JND-190377
PMCID: PMC6597974
PMID: 30958311
Abstract
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.
We aimed to identify genetic variants that are potentially associated with specific clinical outcomes in CMT1A.
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.
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).
While the results require validation in future genetic and functional studies, the detected association signals may point to novel genetic modifiers in CMT1A.
Details
- Title: Subtitle
- Modifier Gene Candidates in Charcot-Marie-Tooth Disease Type 1A: A Case-Only Genome-Wide Association Study
- Creators
- Feifei Tao - Department for Human Genetics and Hussman Institute for Human Genomics, University of Miami, Miami, FL, USAGary W Beecham - Department for Human Genetics and Hussman Institute for Human Genomics, University of Miami, Miami, FL, USAAdriana P Rebelo - Department for Human Genetics and Hussman Institute for Human Genomics, University of Miami, Miami, FL, USASusan H Blanton - Department for Human Genetics and Hussman Institute for Human Genomics, University of Miami, Miami, FL, USAJohn J Moran - Department of Comparative Biosciences and Waisman Center, University of Wisconsin, Madison, WI, USACamila Lopez-Anido - Department of Comparative Biosciences and Waisman Center, University of Wisconsin, Madison, WI, USAJohn Svaren - Department of Comparative Biosciences and Waisman Center, University of Wisconsin, Madison, WI, USALisa Abreu - Department for Human Genetics and Hussman Institute for Human Genomics, University of Miami, Miami, FL, USADevon Rizzo - Data Management and Coordinating Center, Rare Diseases Clinical Research Network, Pediatrics Epidemiology Center, University of South Florida, Tampa, FL, USACallyn A Kirk - Data Management and Coordinating Center, Rare Diseases Clinical Research Network, Pediatrics Epidemiology Center, University of South Florida, Tampa, FL, USAXingyao Wu - Department of Neurology, University of Iowa, Iowa City, IA, USAShawna Feely - Department of Neurology, University of Iowa, Iowa City, IA, USACamiel Verhamme - Department of Neurology, Academic Medical Centre, Amsterdam, The NetherlandsMario A Saporta - Department of Neurology, University of Miami, Miami, FL, USADavid N Herrmann - Department of Neurology, University of Rochester, Rochester, NY, USAJohn W Day - Department of Neurology, Stanford University, Palo Alto, CA, USACharlotte J Sumner - Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USAThomas E Lloyd - Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USAJun Li - Department of Neurology, Wayne State University School of Medicine, Detroit, MI, USASabrina W Yum - Division of Neurology, The Children's Hospital of Philadelphia, Philadelphia, PA, USAFranco Taroni - IRCCS Foundation Carlo Besta Neurological Institute, Milan, ItalyFrank Baas - Department of Clinical Genetics, Leiden University Medical Center, Leiden, The NetherlandsByung-Ok Choi - Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, KoreaDavide Pareyson - IRCCS Foundation Carlo Besta Neurological Institute, Milan, ItalySteven S Scherer - Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USAMary M Reilly - MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology, Queen Square, London, UKMichael E Shy - Department of Neurology, University of Iowa, Iowa City, IA, USAStephan Züchner - Department for Human Genetics and Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA
- Resource Type
- Journal article
- Publication Details
- Journal of neuromuscular diseases, Vol.6(2), pp.201-211
- Publisher
- Netherlands
- DOI
- 10.3233/JND-190377
- PMID
- 30958311
- PMCID
- PMC6597974
- ISSN
- 2214-3599
- eISSN
- 2214-3602
- Grant note
- R01 NS075269 / NINDS NIH HHS R01 NS094388 / NINDS NIH HHS U54 HD090256 / NICHD NIH HHS U54 NS065712 / NINDS NIH HHS R01 NS075764 / NINDS NIH HHS KL2 TR002737 / NCATS NIH HHS R01 NS043174 / NINDS NIH HHS
- Language
- English
- Date published
- 2019
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Stead Family Department of Pediatrics; Iowa Neuroscience Institute
- Record Identifier
- 9984070829902771
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