Zhou, Y and Graves, JS and Simpson, S and Charlesworth, JC and van der Mei, I and Waubant, E and Barcellos, LF and Belman, A and Krupp, L and Lucas, R and Ponsonby, AL and Taylor, BV, Ausimmmune/AusLong investigators group, Genetic variation in the gene LRP2 increases relapse risk in multiple sclerosis, Journal of Neurology, Neurosurgery and Psychiatry, 88, (10) pp. 864-868. ISSN 0022-3050 (2017) [Refereed Article]
Methods: We conducted a genome-wide association analysis (GWAS) to identify genetic variants that predict MS relapse risk, using a three-stage approach. First, GWAS was conducted using the southern Tasmania MS Longitudinal Study with 141 cases followed prospectively for a mean of 2.3 years. Second, GWAS was conducted using the Ausimmune Longitudinal Study with 127 cases having a classic first demyelinating event followed for 5 years from onset. Third, the top hits with p<5.0×10-6 from the first two stages were combined with a longitudinal US paediatric MS cohort with 181 cases followed for 5 years after onset. Predictors of time to relapse were evaluated by a mixed effects Cox model. An inverse variance fixed effects model was then used to undertake a meta-analysis.
Results: In the pooled results, using these three unique longitudinal MS cohorts, we discovered one novel locus (LRP2; most significant single nucleotide polymorphism rs12988804) that reached genome-wide significance in predicting relapse risk (HR=2.18, p=3.30×10-8). LRP2 is expressed on the surface of many central nervous system cells including neurons and oligodendrocytes and is a critical receptor in axonal guidance.
Conclusions: The finding of a genetic locus that has extensive effects on neuronal development and repair is of interest as a potential modulator of MS disease course.
|Item Type:||Refereed Article|
|Keywords:||CNS, LRP2, disease progression, multiple sclerosis, relapse risk|
|Research Division:||Medical and Health Sciences|
|Research Field:||Central Nervous System|
|Objective Group:||Clinical Health (Organs, Diseases and Abnormal Conditions)|
|Objective Field:||Nervous System and Disorders|
|Author:||Zhou, Y (Mr Yuan Zhou)|
|Author:||Simpson, S (Dr Steve Simpson JR)|
|Author:||Charlesworth, JC (Dr Jac Charlesworth)|
|Author:||van der Mei, I (Associate Professor Ingrid van der Mei)|
|Author:||Taylor, BV (Professor Bruce Taylor)|
|Deposited By:||Menzies Institute for Medical Research|
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