Lack of replication of association findings in complex disease: an analysis of 15 polymorphisms in prior candidate genes for sporadic Alzheimer's disease
(2001) In European Journal of Human Genetics 9(6). p.437-444- Abstract
- There is considerable enthusiasm for the prospect of using common polymorphisms (primarily single nucleotide polymorphisms; SNPs) in candidate genes to unravel the genetics of complex disease. This approach has generated a number of findings of loci which are significantly associated with sporadic Alzheimer's disease (AD). In the present study, a total of 15 genes of interest were chosen from among the previously published reports of significant association in AD. Genotyping was performed on polymorphisms within those genes (14 SNPs and one deletion) using Dynamic Allele Specific Hybridization (DASH) in 204 Swedish patients with sporadic late-onset AD and 186 Swedish control subjects. The genes chosen for analysis were; low-density... (More)
- There is considerable enthusiasm for the prospect of using common polymorphisms (primarily single nucleotide polymorphisms; SNPs) in candidate genes to unravel the genetics of complex disease. This approach has generated a number of findings of loci which are significantly associated with sporadic Alzheimer's disease (AD). In the present study, a total of 15 genes of interest were chosen from among the previously published reports of significant association in AD. Genotyping was performed on polymorphisms within those genes (14 SNPs and one deletion) using Dynamic Allele Specific Hybridization (DASH) in 204 Swedish patients with sporadic late-onset AD and 186 Swedish control subjects. The genes chosen for analysis were; low-density lipoprotein receptor-related protein (LRP1), angiotensin converting enzyme (DCP1), alpha-2-macroglobulin (A2M), bleomycin hydrolase (BLMH), dihydrolipoyl S-succinyltransferase (DLST), tumour necrosis factor receptor superfamily member 6 (TNFRSF6), nitric oxide synthase (NOS3), presenilin 1 (PSEN1), presenilin 2 (PSEN2), butyrylcholinesterase (BCHE), Fe65 (APBB1), oestrogen receptor alpha (ESR1), cathepsin D (CTSD), methylenetetrahydrofolate reductase (MTHFR), and interleukin 1A (IL1A). We found no strong evidence of association for any of these loci with AD in this population. While the possibility exists that the genes analysed are involved in AD (ie they have weak effects and/or are population specific), results reinforce the need for extensive replication studies if we are to be successful in defining true risk factors in complex diseases. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1297360
- author
- Prince, J A ; Feuk, L ; Sawyer, S L ; Gottfries, J ; Ricksten, A ; Nägga, Katarina LU ; Bogdanovic, N ; Blennow, K and Brookes, A J
- publishing date
- 2001
- type
- Contribution to journal
- publication status
- published
- subject
- in
- European Journal of Human Genetics
- volume
- 9
- issue
- 6
- pages
- 437 - 444
- publisher
- Nature Publishing Group
- external identifiers
-
- wos:000169522300007
- scopus:0034971263
- ISSN
- 1476-5438
- DOI
- 10.1038/sj.ejhg.5200651
- language
- English
- LU publication?
- no
- id
- 35720504-0149-46a7-b0a1-d46ed14c8f2f (old id 1297360)
- date added to LUP
- 2016-04-01 12:17:53
- date last changed
- 2022-03-28 22:57:02
@article{35720504-0149-46a7-b0a1-d46ed14c8f2f,
abstract = {{There is considerable enthusiasm for the prospect of using common polymorphisms (primarily single nucleotide polymorphisms; SNPs) in candidate genes to unravel the genetics of complex disease. This approach has generated a number of findings of loci which are significantly associated with sporadic Alzheimer's disease (AD). In the present study, a total of 15 genes of interest were chosen from among the previously published reports of significant association in AD. Genotyping was performed on polymorphisms within those genes (14 SNPs and one deletion) using Dynamic Allele Specific Hybridization (DASH) in 204 Swedish patients with sporadic late-onset AD and 186 Swedish control subjects. The genes chosen for analysis were; low-density lipoprotein receptor-related protein (LRP1), angiotensin converting enzyme (DCP1), alpha-2-macroglobulin (A2M), bleomycin hydrolase (BLMH), dihydrolipoyl S-succinyltransferase (DLST), tumour necrosis factor receptor superfamily member 6 (TNFRSF6), nitric oxide synthase (NOS3), presenilin 1 (PSEN1), presenilin 2 (PSEN2), butyrylcholinesterase (BCHE), Fe65 (APBB1), oestrogen receptor alpha (ESR1), cathepsin D (CTSD), methylenetetrahydrofolate reductase (MTHFR), and interleukin 1A (IL1A). We found no strong evidence of association for any of these loci with AD in this population. While the possibility exists that the genes analysed are involved in AD (ie they have weak effects and/or are population specific), results reinforce the need for extensive replication studies if we are to be successful in defining true risk factors in complex diseases.}},
author = {{Prince, J A and Feuk, L and Sawyer, S L and Gottfries, J and Ricksten, A and Nägga, Katarina and Bogdanovic, N and Blennow, K and Brookes, A J}},
issn = {{1476-5438}},
language = {{eng}},
number = {{6}},
pages = {{437--444}},
publisher = {{Nature Publishing Group}},
series = {{European Journal of Human Genetics}},
title = {{Lack of replication of association findings in complex disease: an analysis of 15 polymorphisms in prior candidate genes for sporadic Alzheimer's disease}},
url = {{http://dx.doi.org/10.1038/sj.ejhg.5200651}},
doi = {{10.1038/sj.ejhg.5200651}},
volume = {{9}},
year = {{2001}},
}