Complement receptor 1 gene (CR1) intragenic duplication and risk of Alzheimer’s disease

Kucukkilic, E., Brookes, K. ORCID: 0000-0003-2427-2513, Barber, I., Guetta-Baranes, T., Morgan, K. and Hollox, E.J., 2018. Complement receptor 1 gene (CR1) intragenic duplication and risk of Alzheimer’s disease. Human Genetics, 137 (4), pp. 305-314. ISSN 0340-6717

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Single nucleotide variants (SNVs) within and surrounding the complement receptor 1 (CR1) gene show some of the strongest genome-wide association signals with late-onset Alzheimer’s disease. Some studies have suggested that this association signal is due to a duplication allele (CR1-B) of a low copy repeat (LCR) within the CR1 gene, which increases the number of complement C3b/C4b-binding sites in the mature receptor. In this study, we develop a triplex paralogue ratio test assay for CR1 LCR copy number allowing large numbers of samples to be typed with a limited amount of DNA. We also develop a CR1-B allele-specific PCR based on the junction generated by an historical non-allelic homologous recombination event between CR1 LCRs. We use these methods to genotype CR1 and measure CR1-B allele frequency in both late-onset and early-onset cases and unaffected controls from the United Kingdom. Our data support an association of late-onset Alzheimer’s disease with the CR1-B allele, and confirm that this allele occurs most frequently on the risk haplotype defined by SNV alleles. Furthermore, regression models incorporating CR1-B genotype provide a better fit to our data compared to incorporating the SNV-defined risk haplotype, supporting the CR1-B allele as the variant underlying the increased risk of late-onset Alzheimer’s disease.

Item Type: Journal article
Publication Title: Human Genetics
Creators: Kucukkilic, E., Brookes, K., Barber, I., Guetta-Baranes, T., Morgan, K. and Hollox, E.J.
Publisher: Springer
Date: April 2018
Volume: 137
Number: 4
ISSN: 0340-6717
Rights: © the author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Record created by: Jonathan Gallacher
Date Added: 15 May 2019 09:15
Last Modified: 15 May 2019 09:15

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