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Pathway Analysis of Two Amyotrophic Lateral Sclerosis GWAS Highlights Shared Genetic Signals with Alzheimer’s Disease and Parkinson’s Disease

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Abstract

Amyotrophic lateral sclerosis (ALS) is the third most common neurodegenerative disease after Alzheimer’s disease (AD) and Parkinson’s disease (PD). In order to unravel more genetic etiology of ALS, genome-wide association studies (GWAS) have been conducted. However, the newly identified ALS susceptibility loci exert only very small risk effects and cannot fully explain the underlying ALS genetic risk. A large proportion of the heritability of ALS is still to be explained. Recently, pathway analysis of GWAS has been used to investigate the mechanisms of AD and PD. We think that AD or PD risk pathways may also be involved in ALS. In order to confirm this view, we conducted a pathway analysis of two independent ALS GWAS. We identified multiple classifications of the Kyoto Encyclopedia of Genes and Genomes pathways related to metabolism, immune system and diseases, environmental information processing, genetic information processing, cellular processes, and nervous system and neurodegenerative diseases to be the consistent signals in the two ALS GWAS. On the single pathway level, we identified 12 shared pathways. We compared the findings from ALS GWAS with those of previous pathway analyses of AD and PD GWAS. The results further supported the involvement of AD and PD risk pathways in ALS. We believe that our results may advance the understanding of ALS mechanisms and will be very useful for future genetic studies.

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Acknowledgments

We thank Schymick and Cronin et al. for the ALS GWAS datasets. This work was supported by funding from the National Nature Science Foundation of China (grant numbers 81300945, 81171120, and 81100940).

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Neurology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China

    Hong Shang & Rongrong Song

  2. Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150086, China

    Hong Shang, Jin Fu, Benping Zhang & Weizhi Wang

  3. Genome Analysis Laboratory, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Xiqi Dao 32, Tianjin Airport Economic Area, Tianjin, 300308, China

    Guiyou Liu

  4. College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China

    Yongshuai Jiang

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  1. Hong Shang
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Correspondence to Weizhi Wang.

Additional information

Hong Shang and Guiyou Liu contributed equally to this work.

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Shang, H., Liu, G., Jiang, Y. et al. Pathway Analysis of Two Amyotrophic Lateral Sclerosis GWAS Highlights Shared Genetic Signals with Alzheimer’s Disease and Parkinson’s Disease. Mol Neurobiol 51, 361–369 (2015). https://doi.org/10.1007/s12035-014-8673-1

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