Alzheimer's & Dementia: Research has identified 11 candidate gene variants for Alzheimer's disease

Alzheimer's disease (AD) is the most common, irreversible and progressive form of dementia
.

The "World Report on Alzheimer's Disease 2018" shows that every 3 seconds, 1 person with dementia occurs worldwide

Genetic variation significantly affects the risk of Alzheimer's disease (AD) and is estimated to account for 53% of the total trait variation
.

So far, the genome-wide association study ( GWAS ) for AD has identified more than 30 common mutations that occur in genes

GWAS

Recently, a study co-authored by Dr.
Justin Miller, a researcher at the Sanders-Brown Center for Aging at the University of Kentucky , recently published in Alzheimer's & Dementia, identified 11 rare Alzheimer's disease candidate variants
.

Researchers found 19 different families in Utah who had Alzheimer's disease more frequently than normal

The Alzheimer's & Dementia study identified 11 rare Alzheimer's disease candidate variants

In this study, researchers performed exome sequencing on two cousins ​​from 19 families from high-risk families
.

The Agilent SureSelect XT Human All Exons + UTR (v5) Capture Kit was used to prepare a DNA library from 2 μg DNA per sample

Researchers found 11 rare genetic variants spanning 10 genes, including previously unknown variants in two known Alzheimer's disease risk genes
.

The high-risk cousin pairs affected by AD contain 564 shared rare variants
.

Eleven variants spanning 10 genes are prioritized in the external dataset: rs201665195(ABCA7) and rs28933981(TTR) were previously related to AD pathology; rs141402160(NOTCH3) and rs140914494  (  NOTCH3  ) were previously reported; rs200290640  (  PIDD1  ) And rs199752248  (  PIDD1  ) exist in more than one pair of cousins; rs61729902  (  SNAP91  ),  rs140129800  (  COX6A2  , AC026471 ), and rs191804178 ( MUC16 ) do not exist in a longevity queue; andrs148294193  (  PELI3  ) and rs147599881  (  FCHO1  ) approach significance from the analysis of AD-related phenotypes

Eleven variants spanning 10 genes are prioritized in the external data set: rs201665195  (  ABCA7  ) and rs28933981  (  TTR  ) were previously related to AD pathology; rs201665195 ABCA7 rs28933981 TTR rs141402160 NOTCH3 rs140914494 NOTCH3 rs200290640 PIDD1 rs9161729140178A 191 rs200290640 PIDD1 CO rs1997248140129 AC 191 MUC16 rs148294193 PELI3 rs147599881 FCHO1 PELI3, ABCA7 SNAP91

These analyses support ABCA7 and TTR as AD risk genes, expand the previously reported identification of NOTCH3 variants, and prioritize another seven candidate variants
.

These analyses support ABCA7 and TTR as AD risk genes, expand the previously reported identification of NOTCH3 variants, and prioritize another seven candidate variants
.

ABCA7 TTR NOTCH3

Prioritized variants

Prioritized variants

"Identifying people at increased risk of Alzheimer's disease before they develop symptoms may lead to earlier and more effective interventions," Miller said
.

"In addition, our method of analyzing high-risk lineages can be used to prioritize rare genetic variants that may cause disease

Although this discovery will not immediately affect patient care , identifying genetic variants associated with the disease is the first step in identifying potential drug targets that can be used to develop treatments

Patient care

 

References: Craig C.

References: Craig C.
Teerlink et al, Analysis of high-risk pedigrees identifies 12 candidate variants for Alzheimer's disease,  Alzheimer's & Dementia  (2021).
  DOI: 10.
1002/alz.
12397 Alzheimer's & Dementia DOI: 10.
1002/alz.
12397

 

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