Gene "NPHP1"
Found 1 record
Gene information
Gene symbol:
NPHP1
See related:
Ensembl: ENSG00000144061, Gene ID: 4867
Additive variants :
Undetected
Genetic interaction partners
No data
Modifier statisitcs
Record:
Disorder:
Vriant:
Reference:
Effect type:
Expressivity(1)  
Modifier effect:
Altered onset time(1)  
Detail:
  • Variant 1:
    Gene:
    Genomic location:
    chr2:110983050
    dbSNP ID:
    Target disease:
    Alzheimer's Disease(DOID_10652)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered onset time 
    Evidence:
    P=1.74×10(-12) 
    Effect:
    Novel loci genome-wide significantly associated as modifiers of the age of onset of AD
    Reference:
    Title:
    Pooling/bootstrap-based GWAS (pbGWAS) identifies new loci modifying the age of onset in PSEN1 p.Glu280Ala Alzheimer's disease.
    Species studied:
    Human
    Abstract:
    The literature on GWAS (genome-wide association studies) data suggests that very large sample sizes (for example, 50,000 cases and 50,000 controls) may be required to detect significant associations of genomic regions for complex disorders such as Alzheimer's disease (AD). Because of the challenges of obtaining such large cohorts, we describe here a novel sequential strategy that combines pooling of DNA and bootstrapping (pbGWAS) in order to significantly increase the statistical power and exponentially reduce expenses. We applied this method to a very homogeneous sample of patients belonging to a unique and clinically well-characterized multigenerational pedigree with one of the most severe forms of early onset AD, carrying the PSEN1 p.Glu280Ala mutation (often referred to as E280A mutation), which originated as a consequence of a founder effect. In this cohort, we identified novel loci genome-wide significantly associated as modifiers of the age of onset of AD (CD44, rs187116, P=1.29 × 10; NPHP1, rs10173717, P=1.74 × 10; CADPS2, rs3757536, P=1.54 × 10; GREM2, rs12129547, P=1.69 × 10, among others) as well as other loci known to be associated with AD. Regions identified by pbGWAS were confirmed by subsequent individual genotyping. The pbGWAS methodology and the genes it targeted could provide important insights in determining the genetic causes of AD and other complex conditions.