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Genetic variation in clusterin and risk of dementia and ischemic vascular disease in the general population: cohort studies and meta-analyses of 362,338 individuals

Overview of attention for article published in BMC Medicine, March 2018
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Title
Genetic variation in clusterin and risk of dementia and ischemic vascular disease in the general population: cohort studies and meta-analyses of 362,338 individuals
Published in
BMC Medicine, March 2018
DOI 10.1186/s12916-018-1029-3
Pubmed ID
Authors

Liv Tybjærg Nordestgaard, Anne Tybjærg-Hansen, Katrine Laura Rasmussen, Børge G. Nordestgaard, Ruth Frikke-Schmidt

Abstract

Clusterin, also known as apolipoprotein J (apoJ), is one of the most abundantly expressed apolipoproteins in the brain after apolipoprotein E (apoE). Like the ε4 allele of the apolipoprotein E gene (APOE), the clusterin gene (CLU) is a risk locus for Alzheimer's disease, and may play additional roles in atherosclerosis pathogenesis. We tested whether genetic variation in CLU was associated with either Alzheimer's disease or atherosclerosis-related diseases. We studied individual data on 103,987 participants from the Copenhagen General Population Study (CGPS) and the Copenhagen City Heart Study (CCHS). We genotyped a common CLU variant (rs9331896) and two common APOE variants (rs7412 and rs429358), defining the ε2, ε3, and ε4, alleles in CGPS and CCHS. All individuals in the CGPS and CCHS cohorts were followed from study inclusion to occurrence of event, death, emigration, or until 10 November 2014, whichever came first. Summary consortia data on 258,351 individuals from the International Genomics of Alzheimer's Project (IGAP) and the Coronary Artery Disease Genome-wide Replication and Meta-analysis plus the Coronary Artery Disease (C4D) Genetics and 1000-Genomes-based genome-wide association studies (CARDIoGRAMplusC4D) were used in meta-analyses. In CGPS and CCHS, multifactorially adjusted hazard ratios for Alzheimer's disease, all dementia, vascular dementia, ischemic cerebrovascular disease, and ischemic heart disease were 1.18 (1.07-1.30), 1.09 (1.02-1.17), 0.96 (0.80-1.17), 1.02 (0.97-1.07), and 0.97 (0.93-1.01) per T allele, respectively. Multifactorially adjusted hazard ratios for Alzheimer's disease and all dementia were 2.72 (2.45-3.01) and 2.21 (2.05-2.38) for the APOE ɛ4 allele. There was no interaction between rs9331896 in CLU and rs429358 (defining the ɛ4 allele) in APOE in predicting Alzheimer's disease or all dementia (P = 0.39 and P = 0.21). In a meta-analysis including consortium data, the overall fixed- and random-effects odds ratios for Alzheimer's disease per T allele were 1.16 (1.13-1.18) (I 2 = 0.0%; P for heterogeneity = 0.89). A common variant in CLU was associated with a high risk of Alzheimer's disease and all dementia in the general population but not with vascular dementia or ischemic vascular disease. Important novel aspects compared to previous studies are the incorporation of individual risk factor data, the exact causative ε4 allele, and several subtypes of dementia and atherosclerosis-related endpoints.

Twitter Demographics

The data shown below were collected from the profiles of 2 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 54 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 54 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 12 22%
Student > Bachelor 7 13%
Researcher 6 11%
Student > Ph. D. Student 6 11%
Student > Doctoral Student 3 6%
Other 7 13%
Unknown 13 24%
Readers by discipline Count As %
Medicine and Dentistry 12 22%
Biochemistry, Genetics and Molecular Biology 11 20%
Pharmacology, Toxicology and Pharmaceutical Science 3 6%
Psychology 3 6%
Nursing and Health Professions 2 4%
Other 8 15%
Unknown 15 28%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 26 March 2018.
All research outputs
#12,138,665
of 15,922,425 outputs
Outputs from BMC Medicine
#2,305
of 2,485 outputs
Outputs of similar age
#194,975
of 281,317 outputs
Outputs of similar age from BMC Medicine
#1
of 1 outputs
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