Details

Autor(en) / Beteiligte

• Smith, Rebecca G.
• Hannon, Eilis
• De Jager, Philip L.
• Chibnik, Lori
• Lott, Simon J.
• Condliffe, Daniel
• Smith, Adam R.
• Haroutunian, Vahram
• Troakes, Claire
• Al-Sarraj, Safa
• Bennett, David A.
• Powell, John
• Lovestone, Simon
• Schalkwyk, Leonard
• Mill, Jonathan
• Lunnon, Katie

Titel

Elevated DNA methylation across a 48-kb region spanning the HOXA gene cluster is associated with Alzheimer's disease neuropathology

Ist Teil von

• Alzheimer's & dementia, 2018-12, Vol.14 (12), p.1580-1588

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2018

Quelle

MEDLINE

Beschreibungen/Notizen

• Alzheimer's disease is a neurodegenerative disorder that is hypothesized to involve epigenetic dysregulation of gene expression in the brain. We performed an epigenome-wide association study to identify differential DNA methylation associated with neuropathology in prefrontal cortex and superior temporal gyrus samples from 147 individuals, replicating our findings in two independent data sets (N = 117 and 740). We identify elevated DNA methylation associated with neuropathology across a 48-kb region spanning 208 CpG sites within the HOXA gene cluster. A meta-analysis of the top-ranked probe within the HOXA3 gene (cg22962123) highlighted significant hypermethylation across all three cohorts (P = 3.11 × 10−18). We present robust evidence for elevated DNA methylation associated with Alzheimer's disease neuropathology spanning the HOXA gene cluster on chromosome 7. These data add to the growing evidence highlighting a role for epigenetic variation in Alzheimer's disease, implicating the HOX gene family as a target for future investigation. •We performed an EWAS to identify neuropathology-associated differential DNA methylation in AD.•We identified 10 DMPs that reached experiment-wide significance (P < 2.2 × 10−7) in the prefrontal cortex.•Of 37 Sidak-corrected DMRs identified, six resided in the HOXA gene cluster.•AD-associated hypermethylation spanned >48 kb (208 probes) across the HOXA cluster.•The cortical HOXA DMR was consistently seen across multiple independent data sets.