Apr 5, 2011

Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease

Nature Genetics
Adam C NajGerard Schellenberg

Abstract

The Alzheimer Disease Genetics Consortium (ADGC) performed a genome-wide association study of late-onset Alzheimer disease using a three-stage design consisting of a discovery stage (stage 1) and two replication stages (stages 2 and 3). Both joint analysis and meta-analysis approaches were used. We obtained genome-wide significant results at MS4A4A (rs4938933; stages 1 and 2, meta-analysis P (P(M)) = 1.7 × 10(-9), joint analysis P (P(J)) = 1.7 × 10(-9); stages 1, 2 and 3, P(M) = 8.2 × 10(-12)), CD2AP (rs9349407; stages 1, 2 and 3, P(M) = 8.6 × 10(-9)), EPHA1 (rs11767557; stages 1, 2 and 3, P(M) = 6.0 × 10(-10)) and CD33 (rs3865444; stages 1, 2 and 3, P(M) = 1.6 × 10(-9)). We also replicated previous associations at CR1 (rs6701713; P(M) = 4.6 × 10(-10), P(J) = 5.2 × 10(-11)), CLU (rs1532278; P(M) = 8.3 × 10(-8), P(J) = 1.9 × 10(-8)), BIN1 (rs7561528; P(M) = 4.0 × 10(-14), P(J) = 5.2 × 10(-14)) and PICALM (rs561655; P(M) = 7.0 × 10(-11), P(J) = 1.0 × 10(-10)), but not at EXOC3L2, to late-onset Alzheimer's disease susceptibility.

  • References36
  • Citations544

Citations

Mentioned in this Paper

Genome-Wide Association Study
Familial Alzheimer Disease (FAD)
Receptor, EphA1
Meta-Analysis (Publications)
MS4A8 gene
Leukocyte Differentiation Antigens, Human
EPHA1 gene
PICALM gene
MS4A4A gene
CD2-associated protein

Related Feeds

Alzheimer's Disease: Transcription

Transcription involves copying (transcribing) the gene's DNA sequence into RNA. Impaired transcription is associated with the pathogenesis and progression of conditions such as Alzheimer's disease (AD). Here are the latest discoveries pertaining to transcription and this disease.

Alzheimer's Disease: Genetics

Alzheimer's disease is a chronic neurodegenerative disease. Discover genetic and epigenetic aspects of Alzheimer’s disease, including genetic markers and genomic structural variations here.

Alzheimer's Disease: MS4A

Variants within membrane-spanning 4-domains subfamily A (MS4A) gene cluster have recently been implicated in Alzheimer's disease by recent genome-wide association studies. Here is the latest research.

ALS & FTD: TDP-43

ALS shares with a considerable proportion of FTD cases the same neuropathological substrate, namely, inclusions of abnormally phosphorylated protein tdp-43 (ptdp-43). Here are the latest discoveries pertaining to ptdp-43 and these diseases.

Alzheimer's Disease: Tau & TDP-43

Alzheimer's disease is a chronic neurodegenerative disease. This feed focuses on the underlying role of Tau proteins and TAR DNA-binding protein 43, as well as other genetic factors, in Alzheimer's.

Alzheimer's Disease: RNA Sequencing

RNA sequencing is used to reveal the presence and quantity of RNA in a given sample. In this feed, RNA sequencing investigates the genetic and molecular mechanisms related to the pathophysiology of Alzheimer's disease (AD). Here are the latest discoveries pertaining to RNA sequencing and this disease.

Alzheimer's Disease: Genes&Microglia

Genes and microglia are associated with the risk of developing and the progression of conditions such as Alzheimer's Disease (AD). Here are the latest discoveries pertaining to this disease.

Alpha-Synuclein Structure and Function

α-Synuclein is an integral component of Lewy bodies which are comprised of protein clumps and are a pathological hallmark of Parkinson’s disease. Here is the latest research on α-Synuclein structure and function.

CZI Neurodegeneration Challenge Network

The Neurodegeneration Challenge Network aims to provide funding for and to bring together researchers studying neurodegenerative diseases. Find the latest research from the NDCN grantees here.

Alzheimer's Disease: APOE

Apolipoprotein E (APOE) polymorphic alleles are major genetic risk factors for Alzheimer's Disease. Discover the latest research on APOE and other genetic determinants of Alzheimer's Disease here.

Brain Aging

Here is the latest research on intrinsic and extrinsic factors, as well as pathways and mechanisms that underlie aging in the central nervous system.