Elucidating novel dysfunctional pathways in Alzheimer's disease by integrating loci identified in genetic and epigenetic studies

TY - JOUR

T1 - Elucidating novel dysfunctional pathways in Alzheimer's disease by integrating loci identified in genetic and epigenetic studies

AU - Smith, Adam R.

AU - Mill, Jonathan

AU - Smith, Rebecca G.

AU - Lunnon, Katie

PY - 2016/5/14

Y1 - 2016/5/14

N2 - Alzheimer's disease is a complex neurodegenerative disorder that affected 5.2 million people in America in 2014 (Association, A.S., 2014). A large number of genome-wide association studies (GWAS) have been performed, which have been supplemented more recently by the first epigenome-wide association studies (EWAS), leading to the identification of a number of novel loci altered in disease. Twin studies have shown monozygotic twin discordance for Alzheimer's disease (Mastroeni et al., 2009), leading to the conclusion that a combination of genetic and epigenetic mechanisms are likely to be involved in disease etiology (Lunnon & Mill, 2013). This review focuses on identifying overlapping pathways between published GWAS and EWAS studies, highlighting dysfunctional synaptic, lipid metabolism, plasma membrane/cytoskeleton, mitochondrial and immune cell activation pathways. Identifying common pathways altered in genetic and epigenetic studies will aid our understanding of disease mechanisms and identify potential novel targets for pharmacological intervention.

AB - Alzheimer's disease is a complex neurodegenerative disorder that affected 5.2 million people in America in 2014 (Association, A.S., 2014). A large number of genome-wide association studies (GWAS) have been performed, which have been supplemented more recently by the first epigenome-wide association studies (EWAS), leading to the identification of a number of novel loci altered in disease. Twin studies have shown monozygotic twin discordance for Alzheimer's disease (Mastroeni et al., 2009), leading to the conclusion that a combination of genetic and epigenetic mechanisms are likely to be involved in disease etiology (Lunnon & Mill, 2013). This review focuses on identifying overlapping pathways between published GWAS and EWAS studies, highlighting dysfunctional synaptic, lipid metabolism, plasma membrane/cytoskeleton, mitochondrial and immune cell activation pathways. Identifying common pathways altered in genetic and epigenetic studies will aid our understanding of disease mechanisms and identify potential novel targets for pharmacological intervention.

KW - Alzheimer's disease

KW - AD

KW - DNA methylation

KW - GWAS

KW - EWAS

KW - Exome sequencing

U2 - 10.1016/j.nepig.2016.05.001

DO - 10.1016/j.nepig.2016.05.001

M3 - Article

SN - 2214-7845

JO - Neuroepigenetics

JF - Neuroepigenetics

ER -