Genome-Wide Association Study of Vascular Dementia

Autor: Fernando Rivadeneira, M. Arfan Ikram, Jens Wiltfang, Frank Hentschel, Monique M.B. Breteler, Frank Jessen, Reinhard Heun, Peter J. Koudstaal, Oliver Peters, Eckart Rüther, Heike Kölsch, Albert Hofman, Johannes Kornhuber, Elisabeth M. C. Schrijvers, Wolfgang Maier, Martin Dichgans, Cornelia M. van Duijn, André G. Uitterlinden, Steffi G. Riedel-Heller, Hendrik van den Bussche, Britta Schürmann
Přispěvatelé: Neurology, Epidemiology, Internal Medicine, Radiology & Nuclear Medicine
Rok vydání: 2012
Předmět:
Male
Oncology
Pathology
Medizin
Genome-wide association study
Cohort Studies
Rotterdam Study
Germany
genetics [Chromosomes
Human
X]
Chromosomes
Human
Netherlands
education.field_of_study
Middle Aged
Receptors
Androgen
Female
Alzheimer's disease
Cardiology and Cardiovascular Medicine
Cohort study
medicine.medical_specialty
epidemiology [Dementia
Vascular]
Genotype
Population
epidemiology [Germany]
genetics [Receptors
Androgen]
genetics [Chromosomes
Human]
Polymorphism
Single Nucleotide
Sex Factors
Internal medicine
medicine
Humans
Dementia
ddc:610
education
Vascular dementia
Alleles
Aged
genetics [Dementia
Vascular]
Advanced and Specialized Nursing
Chromosomes
Human
X
genetics [DNA]
business.industry
Dementia
Vascular
DNA
epidemiology [Netherlands]
medicine.disease
Minor allele frequency
Neurology (clinical)
business
Follow-Up Studies
Genome-Wide Association Study
Zdroj: Stroke, 43(2), 315-319. Lippincott Williams & Wilkins
Stroke 43(2), 315-319 (2012). doi:10.1161/STROKEAHA.111.628768
ISSN: 1524-4628
0039-2499
DOI: 10.1161/STROKEAHA.111.628768
Popis: Background and Purpose— Most studies investigating the genetics of dementia have focused on Alzheimer disease, but little is known about the genetics of vascular dementia. The aim of our study was to identify new loci associated with vascular dementia. Methods— We performed a genome-wide association study in the Rotterdam Study, a large prospective population-based cohort study in the Netherlands. We sought to replicate genome-wide significant loci in 2 independent replication samples. Results— In the discovery analysis of 5700 dementia-free individuals, 67 patients developed incident vascular dementia over a mean follow-up time of 9.3±3.2 years. We showed genome-wide significance for rs12007229, which is located on the X chromosome near the androgen receptor gene (OR, 3.7; 95% CI, 2.3–5.8, per copy of the minor allele; P =1.3×10 −8 ). This association was further confirmed in 2 independent populations (probability value of combined replication samples=0.024). Conclusions— Our study shows a novel genetic locus for vascular dementia on the X chromosome. Further replication of this finding is required.
Databáze: OpenAIRE
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