Variant in the sequence of the LINGO1 gene confers risk of essential tremor

Abstract

We identified a marker in LINGO1 showing genome-wide significant association (P = 1.2 x 10(-9), odds ratio = 1.55) with essential tremor. LINGO1 has potent, negative regulatory influences on neuronal survival and is also important in regulating both central-nervous-system axon regeneration and oligodendrocyte maturation. Increased axon integrity observed in Lingo1 mouse [corrected] knockout models highlights the potential role of LINGO1 in the pathophysiology of ET [corrected]

Figure 1

Overview of the 185-kb region around rs9652490. (a) Single marker association results from both the genome-wide scan of Icelandic subjects with essential tremor (red circles) and the combined analysis including four follow-up datasets (blue circles). P values are corrected for relatedness and potential population stratification. (b) Exon structure of the LINGO1 gene. The associated marker is located in intron 3 of the gene. (c) Pairwise correlation coefficient (r²) from the CEU HapMap population.