Journal
EUROPEAN JOURNAL OF HUMAN GENETICS
Volume 18, Issue 7, Pages 838-843Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ejhg.2010.27
Keywords
essential tremor; LINGO1; association; risk factor
Funding
- The National Institutes of Health [R01 NS42859, R01 NS39422, P30 ES009089]
- Parkinson's Disease Foundation (NewYork, NY)
- Columbia University
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A marker in the LINGO1 gene, rs9652490, showing significant genome-wide association with essential tremor (ET), was recently reported in an Icelandic population. To replicate this association in an independent population from North America, we genotyped 15 SNPs in the LINGO1 gene in 257 Caucasian ET cases ('definite,' 'probable' or 'possible') and 265 controls enrolled in an epidemiological study at Columbia University. We observed a marginally significant association with allele G of the marker rs9652490 (P=0.0569, odds ratio (OR)=1.33). However, for 'definite' or 'probable' ET, rs9652490 was significantly associated with ET (P=0.03, OR=1.41). Our subsequent analysis of early-onset ET (age at onset <40 years) revealed that three SNPs, rs177008, rs13313467 and rs8028808, were significantly associated with ET (P=0.028, OR=1.52; P=0.0238, OR=1.54; and P=0.0391, OR=1.55, respectively). These three SNPs represent a 2.3 kb haplotype. Finally, a meta-analysis of three published studies confirms allelic association with rs9652490 and two adjacent SNPs. Our study independently confirms that the LINGO1 gene is a risk factor for ET in a Caucasian population in North America, and further shows that those with early-onset ET are likely to be at high risk. European Journal of Human Genetics (2010) 18, 838-843; doi: 10.1038/ejhg.2010.27; published online 7 April 2010
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