PhenoModifier-Variant Detail

Variant "PICALM:c.1944+4362T>C"

Search result: 1 record

Variant information

Gene:

PICALM

Variant:

PICALM:c.1944+4362T>C

Genomic location:

chr11:85681389(hg19)

HGVS:

SO Term	RefSeq
protein_coding	NM_007166.3:c.1944+4362T>C
protein_coding	NM_001008660.2:c.1818+4362T>C
protein_coding	NM_001206946.1:c.1923+4362T>C
protein_coding	NM_001206947.1:c.1641+4362T>C

dbSNP ID:

rs10501602

GWAS trait:

no data

Modifier statisitcs

Record:

1

Disorder:

1

Reference:

1

Effect type:

Expressivity(1)

Modifier effect:

Altered severity(1)

Detail：

Target disease:

Alzheimer's Disease (DOID_10652)

Effect type:

Expressivity

Modifier effect:

Altered severity

Evidence:

P=0.0102

Effect:

Genetic variation in these new candidate genes affects the risk of late-onset Alzheimer’s disease.

Reference:

PMID22984654

Title:

Beta-amyloid toxicity modifier genes and the risk of Alzheimer's disease.

Species studied:

Human

Abstract:

Late-onset Alzheimer's disease (LOAD) is a complex and multifactorial disease. So far ten loci have been identified for LOAD, including APOE, PICALM, CLU, BIN1, CD2AP, CR1, CD33, EPHA1, ABCA7, and MS4A4A/MS4A6E, but they explain about 50% of the genetic risk and thus additional risk genes need to be identified. Amyloid beta (Aβ) plaques develop in the brains of LOAD patients and are considered to be a pathological hallmark of this disease. Recently 12 new Aβ toxicity modifier genes (ADSSL1, PICALM, SH3KBP1, XRN1, SNX8, PPP2R5C, FBXL2, MAP2K4, SYNJ1, RABGEF1, POMT2, and XPO1) have been identified that potentially play a role in LOAD risk. In this study, we have examined the association of 222 SNPs in these 12 candidate genes with LOAD risk in 1291 LOAD cases and 958 cognitively normal controls. Single site and haplotype analyses were performed using PLINK. Following adjustment for APOE genotype, age, sex, and principal components, we found single nucleotide polymorphisms (SNPs) in PPP2R5C, PICALM, SH3KBP1, XRN1, and SNX8 that showed significant association with risk of LOAD. The top SNP was located in intron 3 of PPP2R5C (P=0.009017), followed by an intron 19 SNP in PICALM (P=0.0102). Haplotype analysis revealed significant associations in ADSSL1, PICALM, PPP2R5C, SNX8, and SH3KBP1 genes. Our data indicate that genetic variation in these new candidate genes affects the risk of LOAD. Further investigation of these genes, including additional replication in other case-control samples and functional studies to elucidate the pathways by which they affect Aβ, are necessary to determine the degree of involvement these genes have for LOAD risk.