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- W2325841306 abstract "The sortilin-related receptor 1 (SORL1) gene has been associated with increased risk for Alzheimer’s disease (AD). Rare genetic variants in the SORL1 gene have also been implicated in autosomal dominant early-onset AD (EOAD). Here we report a large-scale investigation of the contribution of genetic variability in SORL1 to EOAD in a European EOAD cohort. We performed massive parallel amplicon-based re-sequencing of the full coding region of SORL1 in 1255 EOAD patients and 1938 age- and origin-matched control individuals in the context of the European Early-Onset Dementia (EOD) consortium, originating from Belgium, Spain, Portugal, Italy, Sweden, Germany, and Czech Republic. We identified six frameshift variants and two nonsense variants that were exclusively present in patients. These mutations are predicted to result in haploinsufficiency through nonsense-mediated mRNA decay, which could be confirmed experimentally for SORL1 p.Gly447Argfs*22 observed in a Belgian EOAD patient. We observed a 1.5-fold enrichment of rare non-synonymous variants in patients (carrier frequency 8.8 %; SkatOMeta p value 0.0001). Of the 84 non-synonymous rare variants detected in the full patient/control cohort, 36 were only detected in patients. Our findings underscore a role of rare SORL1 variants in EOAD, but also show a non-negligible frequency of these variants in healthy individuals, necessitating the need for pathogenicity assays. Premature stop codons due to frameshift and nonsense variants, have so far exclusively been found in patients, and their predicted mode of action corresponds with evidence from in vitro functional studies of SORL1 in AD." @default.
- W2325841306 created "2016-06-24" @default.
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- W2325841306 date "2016-03-30" @default.
- W2325841306 modified "2023-10-18" @default.
- W2325841306 title "A comprehensive study of the genetic impact of rare variants in SORL1 in European early-onset Alzheimer’s disease" @default.
- W2325841306 cites W1151405824 @default.
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- W2325841306 cites W1732628185 @default.
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- W2325841306 cites W1970706179 @default.
- W2325841306 cites W1984544042 @default.
- W2325841306 cites W1984748656 @default.
- W2325841306 cites W1996675875 @default.
- W2325841306 cites W2008854521 @default.
- W2325841306 cites W2016683781 @default.
- W2325841306 cites W2021341670 @default.
- W2325841306 cites W2029235884 @default.
- W2325841306 cites W2032822445 @default.
- W2325841306 cites W2036963269 @default.
- W2325841306 cites W2058161128 @default.
- W2325841306 cites W2058880763 @default.
- W2325841306 cites W2072870250 @default.
- W2325841306 cites W2086406144 @default.
- W2325841306 cites W2090139525 @default.
- W2325841306 cites W2091861303 @default.
- W2325841306 cites W2095519862 @default.
- W2325841306 cites W2099642610 @default.
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- W2325841306 cites W2103441770 @default.
- W2325841306 cites W2104570606 @default.
- W2325841306 cites W2106623424 @default.
- W2325841306 cites W2107277218 @default.
- W2325841306 cites W2110241845 @default.
- W2325841306 cites W2115017507 @default.
- W2325841306 cites W2115106388 @default.
- W2325841306 cites W2115779804 @default.
- W2325841306 cites W2119180969 @default.
- W2325841306 cites W2119487442 @default.
- W2325841306 cites W2121349242 @default.
- W2325841306 cites W2128228199 @default.
- W2325841306 cites W2129418664 @default.
- W2325841306 cites W2131271579 @default.
- W2325841306 cites W2132040133 @default.
- W2325841306 cites W2137503836 @default.
- W2325841306 cites W2137586531 @default.
- W2325841306 cites W2140729960 @default.
- W2325841306 cites W2143461767 @default.
- W2325841306 cites W2143884110 @default.
- W2325841306 cites W2148080316 @default.
- W2325841306 cites W2150790063 @default.
- W2325841306 cites W2154431968 @default.
- W2325841306 cites W2156220037 @default.
- W2325841306 cites W2159779012 @default.
- W2325841306 cites W2161633633 @default.
- W2325841306 cites W2161815151 @default.
- W2325841306 cites W2167311298 @default.
- W2325841306 cites W2168215272 @default.
- W2325841306 cites W2168656450 @default.
- W2325841306 cites W2170060741 @default.
- W2325841306 cites W2170959965 @default.
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- W2325841306 doi "https://doi.org/10.1007/s00401-016-1566-9" @default.
- W2325841306 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4947104" @default.
- W2325841306 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/27026413" @default.
- W2325841306 hasPublicationYear "2016" @default.
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