Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease

@article{Harold2013GenomewideAS,
  title={Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease},
  author={Denise H. Harold and Richard Abraham and Paul Hollingworth and Rebecca Sims and Amy Gerrish and Marian L. Hamshere and Jaspreet Singh Pahwa and Valentina Moskvina and Kimberley Dowzell and Amy J. Williams and Nicola Jones and Charlene Thomas and Alexandra Stretton and Angharad R. Morgan and Simon Lovestone and John Powell and Petroula Proitsi and Michelle K Lupton and Carol Brayne and David C. Rubinsztein and Michael Gill and Brian A Lawlor and Aoibhinn Lynch and Kevin Morgan and Kristelle S. Brown and Peter Passmore and David Craig and Bernadette McGuinness and Stephen Todd and Clive Holmes and David M A Mann and A. David Smith and Seth Love and Patrick Gavin Kehoe and John Hardy and Simon Mead and Nick C. Fox and Martin N. Rossor and John Collinge and Wolfgang Maier and Frank Jessen and Britta Sch{\"u}rmann and Reinhard Heun and Hendrik van den Bussche and Isabella Heuser and Johannes Kornhuber and Jens Wiltfang and Martin Dichgans and Lutz Fr{\"o}lich and Harald Hampel and Michael H{\"u}ll and Dan Rujescu and Alison M. Goate and John S.K. Kauwe and Carlos Cruchaga and Petra Nowotny and John C. Morris and Kevin Mayo and Kristel Sleegers and Karolien Bettens and Sebastiaan Engelborghs and Peter Paul De Deyn and Christine Van Broeckhoven and Gill Livingston and Nicholas J Bass and Hugh Malcolm Douglas Gurling and Andrew McQuillin and Rhian Gwilliam and Panagiotis Deloukas and Ammar Al-Chalabi and Christopher E. Shaw and Magda Tsolaki and Andrew B. Singleton and Rita Guerreiro and Thomas W. M{\"u}hleisen and Markus M. N{\"o}then and Susanne Moebus and Karl-Heinz J{\"o}ckel and Norman Klopp and Heinz-Erich Wichmann and Minerva M. Carrasquillo and Vernon S Pankratz and Steven G. Younkin and Peter A Holmans and Michael C. O’Donovan and Michael J. Owen and Julie Williams},
  journal={Nature Genetics},
  year={2013},
  volume={45},
  pages={712-712}
}
the 610 group on the Illumina platform. AA, CES, ABS, RG (NIA), TWM, MMN, SM, KJ, NK, HW, MMC, SVP and SGY were involved in clinical sample collection, ascertainment, diagnosis, preparation of samples and genotyping of ‘collaborative samples’ included in Stage 1 (i.e. samples other than the ‘610 group’). KS, KB, SE, PDD, CVB and MT contributed towards sample collection, diagnosis and preparation of case-control material for the stage 2 ‘replication sample’. Replication genotyping was… 

Next generation sequencing of CLU , PICALM and CR 1 : pitfalls and potential solutions

Of the ~170 “novel” variants detected in the genes, seven SNPs, all of which were present in multiple sample pools, were selected for validation by Sanger sequencing and two SNPs were successfully validated by this method, and shown to be genuine variants, while five failed validation.

Implication of common and disease specific variants in CLU, CR1, and PICALM

An Exploratory Study on CLU, CR1 and PICALM and Parkinson Disease

The exploratory analysis suggests an association of CLU with PD, and the role of dementia in explaining this finding needs further investigation.

ATP5H/KCTD2 locus is associated with Alzheimer's disease risk

A novel association with AD is identified in the adenosine triphosphate synthase, H+ transporting, mitochondrial F0 (ATP5H)/Potassium channel tetramerization domain-containing protein 2 (KCTD2) locus, which reached genome-wide significance in the combined discovery and genotyping sample.

Genome-wide haplotype association study identifies the FRMD4A gene as a risk locus for Alzheimer's disease

The characterised FRMD4A as a new genetic risk factor of AD is characterised using a genome-wide haplotype association study and a conservative three-stage replication approach.

PICALM and CR1 variants are not associated with sporadic Alzheimer's disease in Chinese patients.

The frequencies of both of these SNPs were not significantly difference between the SAD and control groups, and the association between SNPs within PICALM, CR1, and SAD should be studied further in different ethnic groups.

Role of CLU, PICALM, and TNK1 Genotypes in Aging With and Without Alzheimer’s Disease

A regression analysis suggested a relationship between age and PICALM genotypes and TNK1 genotypes, with theTNK1-A/A genotype frequency that increased with higher age, and resulting in a different distribution of the TNK 1-A allele.

Association of GWAS Top Genes With Late-Onset Alzheimer’s Disease in Colombian Population

It is shown that APOE variants have a regulatory role on the effect that variants in other loci have on LOAD, reflecting the importance of gene–gene interactions in the etiology of neurodegenerative diseases.
...

References

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Letter abstract - Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's Disease

A two-stage genome-wide association study of Alzheimer's disease involving over 16,000 individuals, the most powerful AD GWAS to date, produced compelling evidence for association with Alzheimer's Disease in the combined dataset.

Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease

A large genome-wide association study of 2,032 individuals from France with Alzheimer's disease and 5,328 controls identified other risk loci, which support roles of CLU and CR1 in the clearance of β amyloid (Aβ) peptide, the principal constituent of amyloids plaques, which are one of the major brain lesions of individuals with Alzheimer’s disease.

Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease, and shows evidence for additional susceptibility genes

A two-stage genome-wide association study of Alzheimer's disease involving over 16,000 individuals, the most powerful AD GWAS to date, produced compelling evidence for association with Alzheimer's Disease in the combined dataset.

A genome-wide association study for late-onset Alzheimer's disease using DNA pooling

The pooling method for GWA studies is validated by both identifying the APOE locus and by observing a strong enrichment for significantly associated SNPs, providing evidence for LRAT as a novel candidate gene for LOAD.

Genetic variation in PCDH11X is associated with susceptibility to late-onset Alzheimer's disease

A SNP (rs5984894) on Xq21.3 in PCDH11X that is strongly associated with LOAD in individuals of European descent from the United States is identified.

Evidence for novel susceptibility genes for late-onset Alzheimer's disease from a genome-wide association study of putative functional variants.

The identification of several candidate SNPs that show significant association with LOAD are reported, several of which map to known linkage regions, biological candidate genes and novel genes.

Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls

This study has demonstrated that careful use of a shared control group represents a safe and effective approach to GWA analyses of multiple disease phenotypes; generated a genome-wide genotype database for future studies of common diseases in the British population; and shown that, provided individuals with non-European ancestry are excluded, the extent of population stratification in theBritish population is generally modest.

Candidate single-nucleotide polymorphisms from a genomewide association study of Alzheimer disease.

The genomewide association analysis again identified the APOE linkage disequilibrium region as the strongest genetic risk factor for AD.

Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes

The results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D, and detect at least six previously unknown loci with robust evidence for association.
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