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A risk prediction algorithm based on family history and common genetic variants: application to prostate cancer with potential clinical impact.

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Date
2011-09
ICR Author
Horwich, Alan
Khoo, Vincent
Dearnaley, David
Eeles, Rosalind
Huddart, Robert
Kote-Jarai, Zsofia
Parker, Chris
van As, Nick
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Author
Macinnis, RJ
Antoniou, AC
Eeles, RA
Severi, G
Al Olama, AA
McGuffog, L
Kote-Jarai, Z
Guy, M
O'Brien, LT
Hall, AL
Wilkinson, RA
Sawyer, E
Ardern-Jones, AT
Dearnaley, DP
Horwich, A
Khoo, VS
Parker, CC
Huddart, RA
Van As, N
McCredie, MR
English, DR
Giles, GG
Hopper, JL
Easton, DF
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Type
Journal Article
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Abstract
Genome wide association studies have identified several single nucleotide polymorphisms (SNPs) that are independently associated with small increments in risk of prostate cancer, opening up the possibility for using such variants in risk prediction. Using segregation analysis of population-based samples of 4,390 families of prostate cancer patients from the UK and Australia, and assuming all familial aggregation has genetic causes, we previously found that the best model for the genetic susceptibility to prostate cancer was a mixed model of inheritance that included both a recessive major gene component and a polygenic component (P) that represents the effect of a large number of genetic variants each of small effect, where . Based on published studies of 26 SNPs that are currently known to be associated with prostate cancer, we have extended our model to incorporate these SNPs by decomposing the polygenic component into two parts: a polygenic component due to the known susceptibility SNPs, , and the residual polygenic component due to the postulated but as yet unknown genetic variants, . The resulting algorithm can be used for predicting the probability of developing prostate cancer in the future based on both SNP profiles and explicit family history information. This approach can be applied to other diseases for which population-based family data and established risk variants exist.
URI
https://repository.icr.ac.uk/handle/internal/1858
DOI
https://doi.org/10.1002/gepi.20605
Collections
  • Closed Research Teams
  • Genetics and Epidemiology
  • Radiotherapy and Imaging
Subject
Humans
Prostatic Neoplasms
Models, Statistical
Probability
Risk
Polymorphism, Single Nucleotide
Algorithms
Models, Genetic
Adult
Aged
Middle Aged
Australia
Male
Genetic Variation
Genome-Wide Association Study
Molecular Epidemiology
United Kingdom
Research team
Clinical Academic Radiotherapy (Dearnaley)
Clinical Academic Radiotherapy (Huddart)
Oncogenetics
Stereotactic and Precision Body Radiotherapy
Language
eng
Date accepted
2011-05-31
License start date
2011-09
Citation
Genetic epidemiology, 2011, 35 (6), pp. 549 - 556

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