Replication of the LINGO1 gene association with essential tremor in a North American population.
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.
Clark
Lorraine N
LN
Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA. lc654@columbia.edu
Park
Naeun
N
Kisselev
Sergey
S
Rios
Eileen
E
Lee
Joseph H
JH
Louis
Elan D
ED
D000328:Adult; D017668:Age of Onset; D000483:Alleles; D001483:Base Sequence; D016022:Case-Control Studies; D003710:Demography; D020329:Essential Tremor / Q000453:epidemiology / Q000235:genetics*; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D015201:Meta-Analysis as Topic; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009656:North America / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015203:Reproducibility of Results
C482293:LINGO1 protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins