Counting potentially functional variants in 
            BRCA1, BRCA2
             and 
            ATM
             predicts breast cancer susceptibility

Johnson, Nichola; Fletcher, Olivia; Palles, Claire; Rudd, Matthew; Webb, Emily L.; Sellick, Gabrielle S.; dos‐Santos‐Silva, Isabel; McCormack, Valerie; Gibson, Lorna; Fraser, Agnes; Leonard, Angela; Gilham, Clare; Tavtigian, Sean V.; Ashworth, Alan; Houlston, Richard S.; Peto, Julian

doi:10.1093/hmg/ddm077

Cited by 28 publications

(35 citation statements)

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“…Wu et al 32 showed that a multigenic analysis of DNA-repair and cell-cycle control genes was efficient at predicting an individual's risk of bladder cancer. Johnson et al 33 demonstrated that a combinatorial study of marginally significant risk alleles in candidate genes was efficient at predicting an individual's risk of breast cancer. Maller et al 34 described the additive action of risk alleles of the CFH, LOC387715 and CFB/C2 loci in genetic susceptibility to age-related macular degeneration.…”

Section: Discussionmentioning

confidence: 99%

Interacting haplotypes at the NPAS3 locus alter risk of schizophrenia and bipolar disorder

et al. 2008

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The neuronal PAS domain 3 (NPAS3) gene encodes a neuronal transcription factor that is implicated in psychiatric disorders by the identification of a human chromosomal translocation associated with schizophrenia and a mouse knockout model with behavioural and hippocampal neurogenesis defects. To determine its contribution to the risk of psychiatric illness in the general population, we genotyped 70 single-nucleotide polymorphisms across the NPAS3 gene in 368 individuals with bipolar disorder, 386 individuals with schizophrenia and 455 controls. Modestly significant single-marker and global and individual haplotypes were identified in four discrete regions of the gene. The presence of both risk and protective haplotypes at each of these four regions indicated locus and allelic heterogeneity within NPAS3 and suggested a model whereby interactions between variants across the gene might contribute to susceptibility to illness. This was supported by predicting the most likely haplotype for each individual at each associated region and then calculating an NPAS3-mediated 'net genetic load' value. This value differed significantly from controls for both bipolar disorder (P = 0.0000010) and schizophrenia (P = 0.0000012). Logistic regression analysis also confirmed the combinatorial action of the four associated regions on disease risk. In addition, sensitivity/specificity plots showed that the extremes of the genetic loading distribution possess the greatest predictive power-a feature suggesting multiplicative allele interaction. These data add to recent evidence that the combinatorial analysis of a number of relatively small effect size haplotypes may have significant power to predict an individual's risk of a complex genetic disorder such as psychiatric illness.

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Section: Discussionmentioning

confidence: 99%

Interacting haplotypes at the NPAS3 locus alter risk of schizophrenia and bipolar disorder

et al. 2008

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show abstract

“…Lastly, we used the published BIC classifications to classify deleterious mutations. However, if unclassified variants of unknown clinical significance in these genes (39)(40)(41) are associated with radiation-induced CBC, we may have underestimated the association.…”

Section: Discussionmentioning

confidence: 99%

Contralateral breast cancer after radiotherapy among BRCA1 and BRCA2 mutation carriers: A WECARE Study Report

Recht¹

2014

Breast Diseases: A Year Book Quarterly

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“…They do not consider the additive pathogenic effect of multiple low-penetrance alleles (Weedon et al, 2006;Johnson et al, 2007) although this needs to be kept under close review. This document does not consider changes that are considered to be clearly pathogenic not requiring any further interpretation, such as frameshift mutations, changes that alter the consensus AG/GT boundaries and nonsense mutations.…”

Section: Scope Of the Guidelinesmentioning

confidence: 99%

Arvelige perifere nevropatier diagnostisert ved dypsekvensering

Høyer¹,

Busk²,

Holla³

et al. 2015

Tidsskriftet

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Counting potentially functional variants in BRCA1, BRCA2 and ATM predicts breast cancer susceptibility

Cited by 28 publications

References 0 publications

Interacting haplotypes at the NPAS3 locus alter risk of schizophrenia and bipolar disorder

Interacting haplotypes at the NPAS3 locus alter risk of schizophrenia and bipolar disorder

Contralateral breast cancer after radiotherapy among BRCA1 and BRCA2 mutation carriers: A WECARE Study Report

Arvelige perifere nevropatier diagnostisert ved dypsekvensering

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