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The Association Between Genetic Variants in SORL1 and Alzheimer Disease in an Urban, Multiethnic, Community-Based Cohort

Joshua H. Lee; Rong Cheng; Nicole Schupf; Jennifer J. Manly; Rafael Antonio Lantigua; Yaakov Stern; Lindsay Farrer; Ekaterina Rogaeva; Yosuke Wakutani; Peter St. George-Hyslop; Richard Paul Mayeux

Title:
The Association Between Genetic Variants in SORL1 and Alzheimer Disease in an Urban, Multiethnic, Community-Based Cohort
Author(s):
Lee, Joshua H.
Cheng, Rong
Schupf, Nicole
Manly, Jennifer J.
Lantigua, Rafael Antonio
Stern, Yaakov
Farrer, Lindsay
Rogaeva, Ekaterina
Wakutani, Yosuke
St. George-Hyslop, Peter
Mayeux, Richard Paul
Date:
Type:
Articles
Department(s):
Taub Institute
Volume:
64
Persistent URL:
Book/Journal Title:
JAMA Neurology
Publisher:
American Medical Association
Abstract:
Objective: To investigate the association between Alzheimer disease (AD) and variant alleles in SORL1 using a series of single nucleotide polymorphisms (SNPs) in an urban, multiethnic, community-based population. Design: We used a nested case-control analysis in a population-based, prospective study of aging and dementia in Medicare recipients, 65 years and older. Setting: Northern Manhattan, NY. Participants: There were 296 patients with probable AD and 428 healthy, elderly controls. The participants were African American (34%), Caribbean Hispanic (51%), or non-Hispanic white (15%). Main Outcome Measures: We genotyped all 29 SNPs in SORL1 that were examined in the earlier report. We assessed allelic association with AD using standard case-control methods, which included apolipoprotein E genotype as a covariate. Results: Several individual SNPs and SNP haplotypes were significantly associated with AD in this prospectively collected community-based cohort, confirming the previously reported positive association of SORL1 with AD. Single nucleotide polymorphism 12, near the 5′ region, was associated with AD in African American and Hispanic individuals. Two SNPs in the 3′ region were also associated with AD in African American (SNP 26) and non-Hispanic white (SNP 20) individuals. A single haplotype in the 3′ region was associated with AD in Hispanic individuals. However, several different haplotypes were associated with AD in African American and white individuals, including the TTC haplotypes at SNPs 23 through 25 (P = .035), which was significantly associated with AD in the North European white individuals in our previous report. Conclusions: This study confirms the association between genetic variants in SORL1 and AD. While the associations observed in these data sets overlap with those previously reported, the finding of novel SNP and haplotype associations suggests that there may be extensive allelic heterogeneity in SORL1. Broad regions of the SORL1 gene will therefore need to be scrutinized for functional pathogenic variants.
Subject(s):
Genetic polymorphisms
Alzheimer's disease
Older people--Mental health
Alzheimer's disease--Genetic aspects
Ethnic groups--Diseases
Dementia
Epidemiology
Genetics
Mental health
Gerontology
Publisher DOI:
https://doi.org/10.1001/archneur.64.4.501
Item views
100
Metadata:
text | xml
Suggested Citation:
Joshua H. Lee, Rong Cheng, Nicole Schupf, Jennifer J. Manly, Rafael Antonio Lantigua, Yaakov Stern, Lindsay Farrer, Ekaterina Rogaeva, Yosuke Wakutani, Peter St. George-Hyslop, Richard Paul Mayeux, , The Association Between Genetic Variants in SORL1 and Alzheimer Disease in an Urban, Multiethnic, Community-Based Cohort, Columbia University Academic Commons, .

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