Alzheimer's disease and age-related macular degeneration have different genetic models for complement gene variation

Petroula Proitsi; Michelle K. Lupton; Frank Dudbridge; Magda Tsolaki; Gillian Hamilton; Makrina Daniilidou; Megan Pritchard; Kathryn Lord; Belinda M. Martin; J. Johnson; David Craig; Stephen Todd; Bernadette McGuinness; Paul Hollingworth; Denise Harold; Iwona Kloszewska; Hilkka Soininen; Patrizia Mecocci; Bruno Velas; Michael Gill; Brian Lawlor; David C. Rubinsztein; Carol Brayne; Peter A. Passmore; Julie Williams; Simon Lovestone; John F. Powell

doi:10.1016/j.neurobiolaging.2011.12.036

Alzheimer's disease and age-related macular degeneration have different genetic models for complement gene variation

Petroula Proitsi, Michelle K. Lupton, Frank Dudbridge, Magda Tsolaki, Gillian Hamilton, Makrina Daniilidou, Megan Pritchard, Kathryn Lord, Belinda M. Martin, J. Johnson, David Craig, Stephen Todd, Bernadette McGuinness, Paul Hollingworth, Denise Harold, Iwona Kloszewska, Hilkka Soininen, Patrizia Mecocci, Bruno Velas, Michael GillBrian Lawlor, David C. Rubinsztein, Carol Brayne, Peter A. Passmore, Julie Williams, Simon Lovestone, John F. Powell

Biological and Biomedical Sciences

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

22 Citations (Scopus)

Abstract

Alzheimer's disease (AD) and age-related macular degeneration (AMD) are both neurodegenerative disorders which share common pathological and biochemical features of the complement pathway. The aim of this study was to investigate whether there is an association between well replicated AMD genetic risk factors and AD. A large cohort of AD (n = 3898) patients and controls were genotyped for single nucleotide polymorphisms (SNPs) in the complement factor H (CFH), the Age-related maculopathy susceptibility protein 2 (ARMS2) the complement component 2 (C2), the complement factor B (CFB), and the complement component 3 (C3) genes. While significant but modest associations were identified between the complement factor H, the age-related maculopathy susceptibility protein 2, and the complement component 3 single nucleotide polymorphisms and AD, these were different in direction or genetic model to that observed in AMD. In addition the multilocus genetic model that predicts around a half of the sibling risk for AMD does not predict risk for AD. Our study provides further support to the hypothesis that while activation of the alternative complement pathway is central to AMD pathogenesis, it is less involved in AD.

Original language	English
Pages (from-to)	1843.e9-17
Journal	Neurobiology of Aging
Volume	33
Issue number	8
Early online date	3 Feb 2012
DOIs	https://doi.org/10.1016/j.neurobiolaging.2011.12.036
Publication status	Published - Aug 2012

Keywords

Alzheimer's disease
age-related macular degeneration
AMD
complement pathway
single nucleotide polymorphism
SNPs
genetic models

Documents and Links

10.1016/j.neurobiolaging.2011.12.036

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Proitsi, P., Lupton, M. K., Dudbridge, F., Tsolaki, M., Hamilton, G., Daniilidou, M., Pritchard, M., Lord, K., Martin, B. M., Johnson, J., Craig, D., Todd, S., McGuinness, B., Hollingworth, P., Harold, D., Kloszewska, I., Soininen, H., Mecocci, P., Velas, B., ... Powell, J. F. (2012). Alzheimer's disease and age-related macular degeneration have different genetic models for complement gene variation. Neurobiology of Aging, 33(8), 1843.e9-17. https://doi.org/10.1016/j.neurobiolaging.2011.12.036

@article{1cad31b0334e4de1a5644cdd8f3c1527,

title = "Alzheimer's disease and age-related macular degeneration have different genetic models for complement gene variation",

abstract = "Alzheimer's disease (AD) and age-related macular degeneration (AMD) are both neurodegenerative disorders which share common pathological and biochemical features of the complement pathway. The aim of this study was to investigate whether there is an association between well replicated AMD genetic risk factors and AD. A large cohort of AD (n = 3898) patients and controls were genotyped for single nucleotide polymorphisms (SNPs) in the complement factor H (CFH), the Age-related maculopathy susceptibility protein 2 (ARMS2) the complement component 2 (C2), the complement factor B (CFB), and the complement component 3 (C3) genes. While significant but modest associations were identified between the complement factor H, the age-related maculopathy susceptibility protein 2, and the complement component 3 single nucleotide polymorphisms and AD, these were different in direction or genetic model to that observed in AMD. In addition the multilocus genetic model that predicts around a half of the sibling risk for AMD does not predict risk for AD. Our study provides further support to the hypothesis that while activation of the alternative complement pathway is central to AMD pathogenesis, it is less involved in AD.",

keywords = "Alzheimer's disease, age-related macular degeneration, AMD, complement pathway, single nucleotide polymorphism, SNPs, genetic models",

author = "Petroula Proitsi and Lupton, {Michelle K.} and Frank Dudbridge and Magda Tsolaki and Gillian Hamilton and Makrina Daniilidou and Megan Pritchard and Kathryn Lord and Martin, {Belinda M.} and J. Johnson and David Craig and Stephen Todd and Bernadette McGuinness and Paul Hollingworth and Denise Harold and Iwona Kloszewska and Hilkka Soininen and Patrizia Mecocci and Bruno Velas and Michael Gill and Brian Lawlor and Rubinsztein, {David C.} and Carol Brayne and Passmore, {Peter A.} and Julie Williams and Simon Lovestone and Powell, {John F.}",

year = "2012",

month = aug,

doi = "10.1016/j.neurobiolaging.2011.12.036",

language = "English",

volume = "33",

pages = "1843.e9--17",

journal = "Neurobiology of Aging",

issn = "0197-4580",

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Proitsi, P, Lupton, MK, Dudbridge, F, Tsolaki, M, Hamilton, G, Daniilidou, M, Pritchard, M, Lord, K, Martin, BM, Johnson, J, Craig, D, Todd, S, McGuinness, B, Hollingworth, P, Harold, D, Kloszewska, I, Soininen, H, Mecocci, P, Velas, B, Gill, M, Lawlor, B, Rubinsztein, DC, Brayne, C, Passmore, PA, Williams, J, Lovestone, S & Powell, JF 2012, 'Alzheimer's disease and age-related macular degeneration have different genetic models for complement gene variation', Neurobiology of Aging, vol. 33, no. 8, pp. 1843.e9-17. https://doi.org/10.1016/j.neurobiolaging.2011.12.036

TY - JOUR

T1 - Alzheimer's disease and age-related macular degeneration have different genetic models for complement gene variation

AU - Proitsi, Petroula

AU - Lupton, Michelle K.

AU - Dudbridge, Frank

AU - Tsolaki, Magda

AU - Hamilton, Gillian

AU - Daniilidou, Makrina

AU - Pritchard, Megan

AU - Lord, Kathryn

AU - Martin, Belinda M.

AU - Johnson, J.

AU - Craig, David

AU - Todd, Stephen

AU - McGuinness, Bernadette

AU - Hollingworth, Paul

AU - Harold, Denise

AU - Kloszewska, Iwona

AU - Soininen, Hilkka

AU - Mecocci, Patrizia

AU - Velas, Bruno

AU - Gill, Michael

AU - Lawlor, Brian

AU - Rubinsztein, David C.

AU - Brayne, Carol

AU - Passmore, Peter A.

AU - Williams, Julie

AU - Lovestone, Simon

AU - Powell, John F.

PY - 2012/8

Y1 - 2012/8

N2 - Alzheimer's disease (AD) and age-related macular degeneration (AMD) are both neurodegenerative disorders which share common pathological and biochemical features of the complement pathway. The aim of this study was to investigate whether there is an association between well replicated AMD genetic risk factors and AD. A large cohort of AD (n = 3898) patients and controls were genotyped for single nucleotide polymorphisms (SNPs) in the complement factor H (CFH), the Age-related maculopathy susceptibility protein 2 (ARMS2) the complement component 2 (C2), the complement factor B (CFB), and the complement component 3 (C3) genes. While significant but modest associations were identified between the complement factor H, the age-related maculopathy susceptibility protein 2, and the complement component 3 single nucleotide polymorphisms and AD, these were different in direction or genetic model to that observed in AMD. In addition the multilocus genetic model that predicts around a half of the sibling risk for AMD does not predict risk for AD. Our study provides further support to the hypothesis that while activation of the alternative complement pathway is central to AMD pathogenesis, it is less involved in AD.

AB - Alzheimer's disease (AD) and age-related macular degeneration (AMD) are both neurodegenerative disorders which share common pathological and biochemical features of the complement pathway. The aim of this study was to investigate whether there is an association between well replicated AMD genetic risk factors and AD. A large cohort of AD (n = 3898) patients and controls were genotyped for single nucleotide polymorphisms (SNPs) in the complement factor H (CFH), the Age-related maculopathy susceptibility protein 2 (ARMS2) the complement component 2 (C2), the complement factor B (CFB), and the complement component 3 (C3) genes. While significant but modest associations were identified between the complement factor H, the age-related maculopathy susceptibility protein 2, and the complement component 3 single nucleotide polymorphisms and AD, these were different in direction or genetic model to that observed in AMD. In addition the multilocus genetic model that predicts around a half of the sibling risk for AMD does not predict risk for AD. Our study provides further support to the hypothesis that while activation of the alternative complement pathway is central to AMD pathogenesis, it is less involved in AD.

KW - Alzheimer's disease

KW - age-related macular degeneration

KW - AMD

KW - complement pathway

KW - single nucleotide polymorphism

KW - SNPs

KW - genetic models

U2 - 10.1016/j.neurobiolaging.2011.12.036

DO - 10.1016/j.neurobiolaging.2011.12.036

M3 - Article

SN - 0197-4580

VL - 33

SP - 1843.e9-17

JO - Neurobiology of Aging

JF - Neurobiology of Aging

IS - 8

ER -

Alzheimer's disease and age-related macular degeneration have different genetic models for complement gene variation

Abstract

Keywords

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