The LDLR locus in alzheimer's disease: A family-based study and meta-analysis of case-control data

Lars Bertram; Monica Hsiao; Matthew B. McQueen; Michele Parkinson; Kristina Mullin; Deborah Blacker; Rudolph E. Tanzi

doi:10.1016/j.neurobiolaging.2005.11.005

The LDLR locus in alzheimer's disease: A family-based study and meta-analysis of case-control data

Lars Bertram, Monica Hsiao, Matthew B. McQueen, Michele Parkinson, Kristina Mullin, Deborah Blacker, Rudolph E. Tanzi

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

Genetic linkage studies suggest the presence of an Alzheimer's disease (AD) risk gene on chromosome 19, acting independently of apolipoprotein E (apoE), a known AD risk factor on 19q13. The low density lipoprotein receptor (LDLR) is an interesting candidate because it maps within the linked interval, and is intimately involved in cholesterol homeostasis and the function of apoE. We tested three previously reported single nucleotide polymorphisms (SNPs) within LDLR in a large sample of discordant sibships from multiplex AD families, and failed to find evidence for genetic association with disease risk. In addition, we performed meta-analyses for SNP rs5925 on published data from five independent case control samples, but did not detect any significant summary odds ratios. Based on our data, it seems unlikely that these genetic variants in LDLR make a significant contribution to AD risk in the general population.

Original language	English
Pages (from-to)	18.e1-18.e4
Journal	Neurobiology of Aging
Volume	28
Issue number	1
DOIs	https://doi.org/10.1016/j.neurobiolaging.2005.11.005
State	Published - Jan 2007
Externally published	Yes

Keywords

LDLR
Low density lipoprotein receptor
Meta-analysis

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10.1016/j.neurobiolaging.2005.11.005

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title = "The LDLR locus in alzheimer's disease: A family-based study and meta-analysis of case-control data",

abstract = "Genetic linkage studies suggest the presence of an Alzheimer's disease (AD) risk gene on chromosome 19, acting independently of apolipoprotein E (apoE), a known AD risk factor on 19q13. The low density lipoprotein receptor (LDLR) is an interesting candidate because it maps within the linked interval, and is intimately involved in cholesterol homeostasis and the function of apoE. We tested three previously reported single nucleotide polymorphisms (SNPs) within LDLR in a large sample of discordant sibships from multiplex AD families, and failed to find evidence for genetic association with disease risk. In addition, we performed meta-analyses for SNP rs5925 on published data from five independent case control samples, but did not detect any significant summary odds ratios. Based on our data, it seems unlikely that these genetic variants in LDLR make a significant contribution to AD risk in the general population.",

keywords = "LDLR, Low density lipoprotein receptor, Meta-analysis",

author = "Lars Bertram and Monica Hsiao and McQueen, {Matthew B.} and Michele Parkinson and Kristina Mullin and Deborah Blacker and Tanzi, {Rudolph E.}",

note = "Funding Information: The authors wish to thank all families for participating in this study. This work was sponsored by grants from the NIMH, NIA and the Alzheimer Association. L.B. is supported by grants from the NIA (1R01 AG023667-01) and a “Young Investigator Award” from the National Alliance for Research on Schizophrenia and Depression (NARSAD). M.B.M. is supported by a National Research Service Award, Training Program in Psychiatric Epidemiology and Biostatistics (T32 MH17119).",

year = "2007",

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T1 - The LDLR locus in alzheimer's disease

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AU - Hsiao, Monica

AU - McQueen, Matthew B.

AU - Parkinson, Michele

AU - Mullin, Kristina

AU - Blacker, Deborah

AU - Tanzi, Rudolph E.

N1 - Funding Information: The authors wish to thank all families for participating in this study. This work was sponsored by grants from the NIMH, NIA and the Alzheimer Association. L.B. is supported by grants from the NIA (1R01 AG023667-01) and a “Young Investigator Award” from the National Alliance for Research on Schizophrenia and Depression (NARSAD). M.B.M. is supported by a National Research Service Award, Training Program in Psychiatric Epidemiology and Biostatistics (T32 MH17119).

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N2 - Genetic linkage studies suggest the presence of an Alzheimer's disease (AD) risk gene on chromosome 19, acting independently of apolipoprotein E (apoE), a known AD risk factor on 19q13. The low density lipoprotein receptor (LDLR) is an interesting candidate because it maps within the linked interval, and is intimately involved in cholesterol homeostasis and the function of apoE. We tested three previously reported single nucleotide polymorphisms (SNPs) within LDLR in a large sample of discordant sibships from multiplex AD families, and failed to find evidence for genetic association with disease risk. In addition, we performed meta-analyses for SNP rs5925 on published data from five independent case control samples, but did not detect any significant summary odds ratios. Based on our data, it seems unlikely that these genetic variants in LDLR make a significant contribution to AD risk in the general population.

AB - Genetic linkage studies suggest the presence of an Alzheimer's disease (AD) risk gene on chromosome 19, acting independently of apolipoprotein E (apoE), a known AD risk factor on 19q13. The low density lipoprotein receptor (LDLR) is an interesting candidate because it maps within the linked interval, and is intimately involved in cholesterol homeostasis and the function of apoE. We tested three previously reported single nucleotide polymorphisms (SNPs) within LDLR in a large sample of discordant sibships from multiplex AD families, and failed to find evidence for genetic association with disease risk. In addition, we performed meta-analyses for SNP rs5925 on published data from five independent case control samples, but did not detect any significant summary odds ratios. Based on our data, it seems unlikely that these genetic variants in LDLR make a significant contribution to AD risk in the general population.

KW - LDLR

KW - Low density lipoprotein receptor

KW - Meta-analysis

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The LDLR locus in alzheimer's disease: A family-based study and meta-analysis of case-control data

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Keywords

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