Sequence variation in the CHAT locus shows no association with late-onset Alzheimer's disease

Denise Harold; Timothy Peirce; Valentina Moskvina; Amanda Myers; Susan Jones; Paul Hollingworth; Pamela Moore; Simon Lovestone; John Powell; Catherine Foy; Nicola Archer; Sarah Walter; Amanda Edmonson; Stephen McIlroy; David Craig; Peter A Passmore; Alison Goate; John Hardy; Michael O'Donovan; Julie Williams; Malcolm Liddell; Michael J Owen; Lesley Jones

doi:10.1007/s00439-003-0960-2

Sequence variation in the CHAT locus shows no association with late-onset Alzheimer's disease

Denise Harold, Timothy Peirce, Valentina Moskvina, Amanda Myers, Susan Jones, Paul Hollingworth, Pamela Moore, Simon Lovestone, John Powell, Catherine Foy, Nicola Archer, Sarah Walter, Amanda Edmonson, Stephen McIlroy, David Craig, Peter A Passmore, Alison Goate, John Hardy, Michael O'Donovan, Julie WilliamsMalcolm Liddell, Michael J Owen, Lesley Jones

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

29 Citations (Scopus)

Abstract

There is substantial evidence for a susceptibility gene for late-onset Alzheimer's disease (AD) on chromosome 10. One of the characteristic features of AD is the degeneration and dysfunction of the cholinergic system. The genes encoding choline acetyltransferase (ChAT) and its vesicular transporter (VAChT), CHAT and SLC18A3 respectively, map to the linked region of chromosome 10 and are therefore both positional and obvious functional candidate genes for late-onset AD. We have screened both genes for sequence variants and investigated each for association with late-onset AD in up to 500 late-onset AD cases and 500 control DNAs collected in the UK. We detected a total of 17 sequence variants. Of these, 14 were in CHAT, comprising three non-synonymous variants (D7N in the S exon, A120T in exon 5 and L243F in exon 8), one synonymous change (H547H), nine single-nucleotide polymorphisms in intronic, untranslated or promoter regions, and a variable number of tandem repeats in intron 7. Three non-coding SNPs were detected in SLC18A3. None demonstrated any reproducible association with late-onset AD in our samples. Levels of linkage disequilibrium were generally low across the CHAT locus but two of the coding variants, D7N and A120T, proved to be in complete linkage disequilibrium.

Original language	English
Pages (from-to)	258-67
Number of pages	10
Journal	Human genetics
Volume	113
Issue number	3
DOIs	https://doi.org/10.1007/s00439-003-0960-2
Publication status	Published - 01 Aug 2003

ASJC Scopus subject areas

Genetics(clinical)
Genetics

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Harold, D., Peirce, T., Moskvina, V., Myers, A., Jones, S., Hollingworth, P., Moore, P., Lovestone, S., Powell, J., Foy, C., Archer, N., Walter, S., Edmonson, A., McIlroy, S., Craig, D., Passmore, P. A., Goate, A., Hardy, J., O'Donovan, M., ... Jones, L. (2003). Sequence variation in the CHAT locus shows no association with late-onset Alzheimer's disease. Human genetics, 113(3), 258-67. https://doi.org/10.1007/s00439-003-0960-2

@article{564bc022f69d4fa09d334452de909ba4,

title = "Sequence variation in the CHAT locus shows no association with late-onset Alzheimer's disease",

abstract = "There is substantial evidence for a susceptibility gene for late-onset Alzheimer's disease (AD) on chromosome 10. One of the characteristic features of AD is the degeneration and dysfunction of the cholinergic system. The genes encoding choline acetyltransferase (ChAT) and its vesicular transporter (VAChT), CHAT and SLC18A3 respectively, map to the linked region of chromosome 10 and are therefore both positional and obvious functional candidate genes for late-onset AD. We have screened both genes for sequence variants and investigated each for association with late-onset AD in up to 500 late-onset AD cases and 500 control DNAs collected in the UK. We detected a total of 17 sequence variants. Of these, 14 were in CHAT, comprising three non-synonymous variants (D7N in the S exon, A120T in exon 5 and L243F in exon 8), one synonymous change (H547H), nine single-nucleotide polymorphisms in intronic, untranslated or promoter regions, and a variable number of tandem repeats in intron 7. Three non-coding SNPs were detected in SLC18A3. None demonstrated any reproducible association with late-onset AD in our samples. Levels of linkage disequilibrium were generally low across the CHAT locus but two of the coding variants, D7N and A120T, proved to be in complete linkage disequilibrium.",

author = "Denise Harold and Timothy Peirce and Valentina Moskvina and Amanda Myers and Susan Jones and Paul Hollingworth and Pamela Moore and Simon Lovestone and John Powell and Catherine Foy and Nicola Archer and Sarah Walter and Amanda Edmonson and Stephen McIlroy and David Craig and Passmore, {Peter A} and Alison Goate and John Hardy and Michael O'Donovan and Julie Williams and Malcolm Liddell and Owen, {Michael J} and Lesley Jones",

year = "2003",

month = aug,

day = "1",

doi = "10.1007/s00439-003-0960-2",

language = "English",

volume = "113",

pages = "258--67",

journal = "Human genetics",

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publisher = "Springer Science and Business Media Deutschland GmbH",

number = "3",

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Harold, D, Peirce, T, Moskvina, V, Myers, A, Jones, S, Hollingworth, P, Moore, P, Lovestone, S, Powell, J, Foy, C, Archer, N, Walter, S, Edmonson, A, McIlroy, S, Craig, D, Passmore, PA, Goate, A, Hardy, J, O'Donovan, M, Williams, J, Liddell, M, Owen, MJ & Jones, L 2003, 'Sequence variation in the CHAT locus shows no association with late-onset Alzheimer's disease', Human genetics, vol. 113, no. 3, pp. 258-67. https://doi.org/10.1007/s00439-003-0960-2

TY - JOUR

T1 - Sequence variation in the CHAT locus shows no association with late-onset Alzheimer's disease

AU - Harold, Denise

AU - Peirce, Timothy

AU - Moskvina, Valentina

AU - Myers, Amanda

AU - Jones, Susan

AU - Hollingworth, Paul

AU - Moore, Pamela

AU - Lovestone, Simon

AU - Powell, John

AU - Foy, Catherine

AU - Archer, Nicola

AU - Walter, Sarah

AU - Edmonson, Amanda

AU - McIlroy, Stephen

AU - Craig, David

AU - Passmore, Peter A

AU - Goate, Alison

AU - Hardy, John

AU - O'Donovan, Michael

AU - Williams, Julie

AU - Liddell, Malcolm

AU - Owen, Michael J

AU - Jones, Lesley

PY - 2003/8/1

Y1 - 2003/8/1

N2 - There is substantial evidence for a susceptibility gene for late-onset Alzheimer's disease (AD) on chromosome 10. One of the characteristic features of AD is the degeneration and dysfunction of the cholinergic system. The genes encoding choline acetyltransferase (ChAT) and its vesicular transporter (VAChT), CHAT and SLC18A3 respectively, map to the linked region of chromosome 10 and are therefore both positional and obvious functional candidate genes for late-onset AD. We have screened both genes for sequence variants and investigated each for association with late-onset AD in up to 500 late-onset AD cases and 500 control DNAs collected in the UK. We detected a total of 17 sequence variants. Of these, 14 were in CHAT, comprising three non-synonymous variants (D7N in the S exon, A120T in exon 5 and L243F in exon 8), one synonymous change (H547H), nine single-nucleotide polymorphisms in intronic, untranslated or promoter regions, and a variable number of tandem repeats in intron 7. Three non-coding SNPs were detected in SLC18A3. None demonstrated any reproducible association with late-onset AD in our samples. Levels of linkage disequilibrium were generally low across the CHAT locus but two of the coding variants, D7N and A120T, proved to be in complete linkage disequilibrium.

AB - There is substantial evidence for a susceptibility gene for late-onset Alzheimer's disease (AD) on chromosome 10. One of the characteristic features of AD is the degeneration and dysfunction of the cholinergic system. The genes encoding choline acetyltransferase (ChAT) and its vesicular transporter (VAChT), CHAT and SLC18A3 respectively, map to the linked region of chromosome 10 and are therefore both positional and obvious functional candidate genes for late-onset AD. We have screened both genes for sequence variants and investigated each for association with late-onset AD in up to 500 late-onset AD cases and 500 control DNAs collected in the UK. We detected a total of 17 sequence variants. Of these, 14 were in CHAT, comprising three non-synonymous variants (D7N in the S exon, A120T in exon 5 and L243F in exon 8), one synonymous change (H547H), nine single-nucleotide polymorphisms in intronic, untranslated or promoter regions, and a variable number of tandem repeats in intron 7. Three non-coding SNPs were detected in SLC18A3. None demonstrated any reproducible association with late-onset AD in our samples. Levels of linkage disequilibrium were generally low across the CHAT locus but two of the coding variants, D7N and A120T, proved to be in complete linkage disequilibrium.

U2 - 10.1007/s00439-003-0960-2

DO - 10.1007/s00439-003-0960-2

M3 - Article

C2 - 12759818

SN - 1432-1203

VL - 113

SP - 258

EP - 267

JO - Human genetics

JF - Human genetics

IS - 3

ER -

Sequence variation in the CHAT locus shows no association with late-onset Alzheimer's disease

Abstract

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