Home > Publications Database > Exome sequencing identifies rare damaging variants in ATP8B4 and ABCA1 as risk factors for Alzheimer's disease. > print

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024 7 _ |a pmc:PMC9729101
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024 7 _ |a 10.1038/s41588-022-01208-7
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024 7 _ |a pmid:36411364
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024 7 _ |a 1061-4036
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024 7 _ |a 1546-1718
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024 7 _ |a altmetric:138726515
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037 _ _ |a DZNE-2022-01745
041 _ _ |a English
082 _ _ |a 570
100 1 _ |a Holstege, Henne
|0 0000-0002-7688-3087
|b 0
245 _ _ |a Exome sequencing identifies rare damaging variants in ATP8B4 and ABCA1 as risk factors for Alzheimer's disease.
260 _ _ |a London
|c 2022
|b Macmillan Publishers Limited, part of Springer Nature
336 7 _ |a article
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336 7 _ |a ARTICLE
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336 7 _ |a Journal Article
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520 _ _ |a Alzheimer's disease (AD), the leading cause of dementia, has an estimated heritability of approximately 70%1. The genetic component of AD has been mainly assessed using genome-wide association studies, which do not capture the risk contributed by rare variants2. Here, we compared the gene-based burden of rare damaging variants in exome sequencing data from 32,558 individuals-16,036 AD cases and 16,522 controls. Next to variants in TREM2, SORL1 and ABCA7, we observed a significant association of rare, predicted damaging variants in ATP8B4 and ABCA1 with AD risk, and a suggestive signal in ADAM10. Additionally, the rare-variant burden in RIN3, CLU, ZCWPW1 and ACE highlighted these genes as potential drivers of respective AD-genome-wide association study loci. Variants associated with the strongest effect on AD risk, in particular loss-of-function variants, are enriched in early-onset AD cases. Our results provide additional evidence for a major role for amyloid-β precursor protein processing, amyloid-β aggregation, lipid metabolism and microglial function in AD.
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650 _ 7 |a ABCA1 protein, human
|2 NLM Chemicals
650 _ 7 |a Adenosine Triphosphatases
|0 EC 3.6.1.-
|2 NLM Chemicals
650 _ 7 |a ATP Binding Cassette Transporter 1
|2 NLM Chemicals
650 _ 7 |a ATP8B4 protein, human
|0 EC 3.6.1.-
|2 NLM Chemicals
650 _ 7 |a SORL1 protein, human
|2 NLM Chemicals
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Adenosine Triphosphatases: genetics
|2 MeSH
650 _ 2 |a Alzheimer Disease: genetics
|2 MeSH
650 _ 2 |a ATP Binding Cassette Transporter 1: genetics
|2 MeSH
650 _ 2 |a Genome-Wide Association Study
|2 MeSH
650 _ 2 |a Risk Factors
|2 MeSH
650 _ 2 |a Exosomes: genetics
|2 MeSH
700 1 _ |a Hulsman, Marc
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773 _ _ |a 10.1038/s41588-022-01208-7
|g Vol. 54, no. 12, p. 1786 - 1794
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787 0 _ |a Holstege, Henne et.al.
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|t Summary statistics for 'Exome sequencing identifies rare damaging variants in ATP8B4 and ABCA1 as risk factors for Alzheimer's Disease'
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