Publication year
2011Source
American Journal of Psychiatry, 168, 10, (2011), pp. 1083-1089ISSN
Publication type
Article / Letter to editor

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Organization
Cognitive Neuroscience
Human Genetics
Psychiatry
Neurology
Nuclear Medicine
Journal title
American Journal of Psychiatry
Volume
vol. 168
Issue
iss. 10
Page start
p. 1083
Page end
p. 1089
Subject
DCN 1: Perception and Action; DCN 2: Functional Neurogenomics; IGMD 3: Genomic disorders and inherited multi-system disorders; IGMD 3: Genomic disorders and inherited multi-system disorders DCN 2: Functional Neurogenomics; NCMLS 6: Genetics and epigenetic pathways of disease IGMD 3: Genomic disorders and inherited multi-system disordersAbstract
OBJECTIVE: Alzheimer's disease is among the most common neurodegenerative disorders. The SORL1 (sortilin receptor 1) gene is associated with the disease, but different variants seem to contribute. The authors used a gene-wide approach to test whether SORL1 is associated with volume of the hippocampus, one of the first structures to be affected by Alzheimer's disease in young, healthy individuals, in an attempt to map potential pathways from gene to disease. METHOD: Individuals were genotyped using an array-based method, and a total of 117 single nucleotide polymorphisms (SNPs) in and surrounding SORL1 were included in the analysis. Through the use of a brain segmentation protocol, SNP-by-SNP and gene-wide associations with bilateral hippocampal volume were assessed in two large, independent samples consisting of 446 (discovery cohort) and 490 (replication cohort) healthy young individuals. RESULTS: Significant association of the SORL1 gene with hippocampal volume was observed in both the discovery and replication samples as well as in the combined sample. The gene-wide association was independent of the apolipoprotein E genotype and resistant to removal of four significantly associated single SNPs. CONCLUSIONS: This study provides the first evidence that the SORL1 gene is associated with differences in hippocampal volume in young, healthy adults. It is demonstrated that gene-wide analysis techniques may overcome power problems caused by allelic heterogeneity in association studies. The results support the hypothesis that the SORL1 gene contributes to an increased risk for Alzheimer's disease through effects on hippocampal volume.
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- Academic publications [205173]
- Faculty of Medical Sciences [81055]
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