EIF3G is associated with narcolepsy across ethnicities.

Abstract	Type 1 narcolepsy, an autoimmune disease affecting hypocretin (orexin) neurons, is strongly associated with HLA-DQB106:02. Among polymorphisms associated with the disease is single-nucleotide polymorphism rs2305795 (c.638G>A) located within the P2RY11 gene. P2RY11 is in a region of synteny conserved in mammals and zebrafish containing PPAN, EIF3G and DNMT1 (DNA methyltransferase 1). As mutations in DNMT1 cause a rare dominant form of narcolepsy in association with deafness, cerebellar ataxia and dementia, we questioned whether the association with P2RY11 in sporadic narcolepsy could be secondary to linkage disequilibrium with DNMT1. Based on genome-wide association data from two cohorts of European and Chinese ancestry, we found that the narcolepsy association signal drops sharply between P2RY11/EIF3G and DNMT1, suggesting that the association with narcolepsy does not extend into the DNMT1 gene region. Interestingly, using transethnic mapping, we identified a novel single-nucleotide polymorphism rs3826784 (c.596-260A>G) in the EIF3G gene also associated with narcolepsy. The disease-associated allele increases EIF3G mRNA expression. EIF3G is located in the narcolepsy risk locus and EIF3G expression correlates with PPAN and P2RY11 expression. This suggests shared regulatory mechanisms that might be affected by the polymorphism and are of relevance to narcolepsy.
Authors	Anja Holm, Ling Lin, Juliette Faraco, Sara Mostafavi, Alexis Battle, Xiaowei Zhu, Douglas F Levinson, Fang Han, Steen Gammeltoft, Poul Jennum, Emmanuel Mignot, Birgitte R Kornum
Journal	European journal of human genetics : EJHG (Eur J Hum Genet) Vol. 23 Issue 11 Pg. 1573-80 (Nov 2015) ISSN: 1476-5438 [Electronic] England
PMID	25669430 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	Eukaryotic Initiation Factor-3 HLA-DQ beta-Chains HLA-DQB1 antigen Nuclear Proteins P2RY11 protein, human PPAN protein, human Receptors, Purinergic P2 DNA (Cytosine-5-)-Methyltransferase 1 DNA (Cytosine-5-)-Methyltransferases DNMT1 protein, human
Topics	Alleles Animals DNA (Cytosine-5-)-Methyltransferase 1 DNA (Cytosine-5-)-Methyltransferases (genetics) Ethnicity (genetics) Eukaryotic Initiation Factor-3 (biosynthesis, genetics) Female Gene Expression Regulation Genetic Predisposition to Disease Genome-Wide Association Study HLA-DQ beta-Chains (genetics) Humans Male Mutation Narcolepsy (genetics, pathology) Nuclear Proteins (biosynthesis, genetics) Polymorphism, Single Nucleotide Receptors, Purinergic P2 (biosynthesis, genetics)

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