TY - JOUR
T1 - Replication of the LINGO1 gene association with essential tremor in a North American population
AU - Clark, Lorraine N.
AU - Park, Naeun
AU - Kisselev, Sergey
AU - Rios, Eileen
AU - Lee, Joseph H.
AU - Louis, Elan D.
N1 - Funding Information:
This study was supported by The National Institutes of Health (R01 NS42859 to EDL, R01 NS39422 to EDL and P30 ES009089 to EDL), the Parkinson’s Disease Foundation (New York, NY) to EDL and LNC and the Arlene Bronstein Essential Tremor Research Fund (Columbia University) to EDL. Technical support was provided by Prashanthi Maramreddy (Columbia University).
PY - 2010/7
Y1 - 2010/7
N2 - 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, OR1.41). 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, OR1.54; 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.
AB - 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, OR1.41). 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, OR1.54; 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.
KW - Association
KW - Essential tremor
KW - LINGO1
KW - Risk factor
UR - http://www.scopus.com/inward/record.url?scp=77953807518&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77953807518&partnerID=8YFLogxK
U2 - 10.1038/ejhg.2010.27
DO - 10.1038/ejhg.2010.27
M3 - Article
C2 - 20372186
AN - SCOPUS:77953807518
SN - 1018-4813
VL - 18
SP - 838
EP - 843
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 7
ER -