SORL1 variants and risk of late-onset Alzheimer's disease

Yonghong Li; Charles Rowland; Joseph Catanese; John Morris; Simon Lovestone; Michael C. O'Donovan; Alison Goate; Michael Owen; Julie Williams; Andrew Grupe

doi:10.1016/j.nbd.2007.09.001

SORL1 variants and risk of late-onset Alzheimer's disease

Yonghong Li
, Charles Rowland
, Joseph Catanese
, John Morris
, Simon Lovestone
, Michael C. O'Donovan
, Alison Goate
, Michael Owen
, Julie Williams
, Andrew Grupe

Research output: Contribution to journal › Article › peer-review

70 Scopus citations

Abstract

A recent study reported significant association of late-onset Alzheimer's disease (LOAD) with multiple single nucleotide polymorphisms (SNPs) and haplotypes in SORL1, a neuronal sortilin-related receptor protein known to be involved in the trafficking and processing of amyloid precursor protein. Here we attempted to validate this finding in three large, well characterized case-control series. Approximately 2000 samples from the three series were individually genotyped for 12 SNPs, including the 10 reported significant SNPs and 2 that constitute the reported significant haplotypes. A total of 25 allelic and haplotypic association tests were performed. One SNP rs2070045 was marginally replicated in the three sample sets combined (nominal P = 0.035); however, this result does not remain significant when accounting for multiple comparisons. Further validation in other sample sets will be required to assess the true effects of SORL1 variants in LOAD.

Original language	English
Pages (from-to)	293-296
Number of pages	4
Journal	Neurobiology of Disease
Volume	29
Issue number	2
DOIs	https://doi.org/10.1016/j.nbd.2007.09.001
State	Published - Feb 2008

Keywords

Alzheimer's disease
Association study
Haplotype
SORL1
Single nucleotide polymorphism

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10.1016/j.nbd.2007.09.001

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@article{3ee5c52c9a044bd59d37372ef17edf98,

title = "SORL1 variants and risk of late-onset Alzheimer's disease",

abstract = "A recent study reported significant association of late-onset Alzheimer's disease (LOAD) with multiple single nucleotide polymorphisms (SNPs) and haplotypes in SORL1, a neuronal sortilin-related receptor protein known to be involved in the trafficking and processing of amyloid precursor protein. Here we attempted to validate this finding in three large, well characterized case-control series. Approximately 2000 samples from the three series were individually genotyped for 12 SNPs, including the 10 reported significant SNPs and 2 that constitute the reported significant haplotypes. A total of 25 allelic and haplotypic association tests were performed. One SNP rs2070045 was marginally replicated in the three sample sets combined (nominal P = 0.035); however, this result does not remain significant when accounting for multiple comparisons. Further validation in other sample sets will be required to assess the true effects of SORL1 variants in LOAD.",

keywords = "Alzheimer's disease, Association study, Haplotype, SORL1, Single nucleotide polymorphism",

author = "Yonghong Li and Charles Rowland and Joseph Catanese and John Morris and Simon Lovestone and O'Donovan, \{Michael C.\} and Alison Goate and Michael Owen and Julie Williams and Andrew Grupe",

note = "Funding Information: We thank the families/individuals for their invaluable participation in this study and our colleagues for expert technical contributions. We acknowledge Pamela Moore and Dragana Turic for providing clinical/DNA samples from the MRC UK Genetic Resource for LOAD and Mary Coats and Elizabeth Grant for coordinating the Washington University material. Funding for this work was partly provided by the Medical Research Council, UK, and the Alzheimer{\textquoteright}s Research Trust to J.W., M.O., M.O{\textquoteright}D., and S.L., and the National Institute of Health grants P50 AG05681 and PO1 AG03991 to J.M. and RO1 AG16208 to A. Goate. Statement of conflict of interest: Y.L., C.R., J.C., and A. Grupe are employed by Celera. A. Goate received research funding from and was a consultant to Celera. M.O. and J.W. received research funding from Celera.",

year = "2008",

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doi = "10.1016/j.nbd.2007.09.001",

language = "English",

volume = "29",

pages = "293--296",

journal = "Neurobiology of Disease",

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AU - Li, Yonghong

AU - Rowland, Charles

AU - Catanese, Joseph

AU - Morris, John

AU - Lovestone, Simon

AU - O'Donovan, Michael C.

AU - Goate, Alison

AU - Owen, Michael

AU - Williams, Julie

AU - Grupe, Andrew

N1 - Funding Information: We thank the families/individuals for their invaluable participation in this study and our colleagues for expert technical contributions. We acknowledge Pamela Moore and Dragana Turic for providing clinical/DNA samples from the MRC UK Genetic Resource for LOAD and Mary Coats and Elizabeth Grant for coordinating the Washington University material. Funding for this work was partly provided by the Medical Research Council, UK, and the Alzheimer’s Research Trust to J.W., M.O., M.O’D., and S.L., and the National Institute of Health grants P50 AG05681 and PO1 AG03991 to J.M. and RO1 AG16208 to A. Goate. Statement of conflict of interest: Y.L., C.R., J.C., and A. Grupe are employed by Celera. A. Goate received research funding from and was a consultant to Celera. M.O. and J.W. received research funding from Celera.

PY - 2008/2

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N2 - A recent study reported significant association of late-onset Alzheimer's disease (LOAD) with multiple single nucleotide polymorphisms (SNPs) and haplotypes in SORL1, a neuronal sortilin-related receptor protein known to be involved in the trafficking and processing of amyloid precursor protein. Here we attempted to validate this finding in three large, well characterized case-control series. Approximately 2000 samples from the three series were individually genotyped for 12 SNPs, including the 10 reported significant SNPs and 2 that constitute the reported significant haplotypes. A total of 25 allelic and haplotypic association tests were performed. One SNP rs2070045 was marginally replicated in the three sample sets combined (nominal P = 0.035); however, this result does not remain significant when accounting for multiple comparisons. Further validation in other sample sets will be required to assess the true effects of SORL1 variants in LOAD.

AB - A recent study reported significant association of late-onset Alzheimer's disease (LOAD) with multiple single nucleotide polymorphisms (SNPs) and haplotypes in SORL1, a neuronal sortilin-related receptor protein known to be involved in the trafficking and processing of amyloid precursor protein. Here we attempted to validate this finding in three large, well characterized case-control series. Approximately 2000 samples from the three series were individually genotyped for 12 SNPs, including the 10 reported significant SNPs and 2 that constitute the reported significant haplotypes. A total of 25 allelic and haplotypic association tests were performed. One SNP rs2070045 was marginally replicated in the three sample sets combined (nominal P = 0.035); however, this result does not remain significant when accounting for multiple comparisons. Further validation in other sample sets will be required to assess the true effects of SORL1 variants in LOAD.

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KW - Association study

KW - Haplotype

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KW - Single nucleotide polymorphism

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ER -

SORL1 variants and risk of late-onset Alzheimer's disease

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Keywords

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