MGMT as a novel risk gene for Alzheimer's disease among women

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MGMT as a novel risk gene for Alzheimer's disease among women

Post by circular »

CNN reported on this paper published yesterday.

Genome-wide association and multi-omics studies identify MGMT as a novel risk gene for Alzheimer's disease among women

We identified novel associations of AD with MGMT variants in the ADGC (rs12775171, odds ratio [OR] = 1.4, P = 4.9 × 10–8) and Hutterite (rs12256016 and rs2803456, OR = 2.0, P = 1.9 × 10–14) datasets. Multi-omics analyses showed that the most significant and largest number of associations among the single nucleotide polymorphisms (SNPs), DNA-methylated CpGs, MGMT expression, and AD-related neuropathological traits were observed among women. Furthermore, promoter capture Hi-C analyses revealed long-range interactions of the MGMT promoter with MGMT SNPs and CpG sites.


These findings suggest that epigenetically regulated MGMT expression is involved in AD pathogenesis, especially in women.

We identified a novel association of AD with genetic variants in MGMT among women lacking the APOE ε4 allele in the ADGC cohorts and with genetic variants within and upstream of MGMT in Hutterite women regardless of APOE ε4 carrier status. Multi-omics analysis suggested that epigenetically regulated expression of MGMT, which is involved in DNA damage repair function, is significantly associated with the development of the hallmark AD proteins, Aβ and tau, especially in women. [Emphasis added]
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Re: MGMT as a novel risk gene for Alzheimer's disease among women

Post by mike »

I would think this study could also likely point to the reason

Brain Changes Diverge Between Men and Women
— White matter hyperintensities volume accelerate after menopause ... definition
White matter hyperintensities -- small brain lesions associated with cognitive impairment or stroke risk -- were more common in post-menopausal women than they were in men of similar age, cross-sectional data showed.

Premenopausal women and men of the same age, however, had no difference in white matter hyperintensities burden, according to Monique Breteler, MD, PhD, of the German Center of Neurodegenerative Diseases in Bonn, and co-authors.
Sonoma Mike
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