Methods of analysis of polymorphisms and uses thereof

Abstract

The present invention provides methods for the assessment of diseases that result from the combined or interactive effects of two or more genetic variants, and in particular for diagnosing risk of developing such diseases in subjects using an analysis of genetic polymorphisms. Methods for the derivation of a net score indicative of a subject's risk of developing a disease are provided.

1 . A method of assessing a subject's risk of developing a disease which comprises:
 analysing a biological sample from said subject for the presence or absence of a protective polymorphism and for the presence or absence of a susceptibility polymorphism, wherein said protective polymorphism and said susceptibility polymorphism are associated with said disease;   assigning a positive score for each protective polymorphism and a negative score for each susceptibility polymorphism or vice versa;   calculating a net score for said subject, said net score representing the balance between the combined value of the protective polymorphism and the combined value of the susceptibility polymorphism present in the subject sample;   wherein a net protective score is predictive of a reduced risk of developing said disease and a net susceptibility score is predictive of an increased risk of developing said disease.   
     
     
         2 . A method according to  claim 1  wherein the value assigned to each protective polymorphism is the same. 
     
     
         3 .- 25 . (canceled) 
     
     
         26 . A method of determining a subject's risk of developing a disease, said method comprising:
 obtaining the result of one or more analyses of a sample from said subject to determine a presence or absence of a protective polymorphism and a presence or absence of a susceptibility polymorphism, and wherein said protective and susceptibility polymorphisms are associated with said disease;   assigning a positive score for each protective polymorphism and a negative score for each susceptibility polymorphism or vice versa; and   calculating a net score for said subject, said net score representing a balance between a combined value of the protective polymorphism and a combined value of the susceptibility polymorphism present in the subject sample,   wherein a net protective score is predictive of a reduced risk of developing said disease and a net susceptibility score is predictive of an increased risk of developing said disease.   
     
     
         27 . (canceled) 
     
     
         28 . A method of treatment of a subject to decrease a risk of developing a disease through alteration of the net score for said subject as determined by a method as defined above, wherein said method of treatment comprises:
 reversing, genotypically or phenotypically, the presence and/or functional effect of one or more susceptibility polymorphisms associated with said disease; and/or   replicating and/or mimicking, genotypically or phenotypically, the presence and/or functional effect of one or more protective polymorphisms associated with said disease   3) a) reversing, genotypically or phenotypically, the presence, functional effect, or presence and functional effect of one or more susceptibility polymorphisms associated with said disease and
 b) replicating, mimicking, or replicating and mimicking, genotypically or phenotypically, the presence, functional effect, or presence and functional effect of one or more protective polymorphisms associated with said disease. 
   
     
     
         29 . (canceled)