Method and kit for genetic analysis

Abstract

Methods and kits for assessing severity index for alcohol abuse, drug abuse, and other reward deficiency syndromes. It has been discovered that a multifaceted non-specific RDS behaviors should be considered as the true “reward” phenotype (endophenotype) instead of a single subset RDS behavior such as alcoholism. In an embodiment of the present invention, it has been discovered that there are at least eleven risk alleles associated with ten candidate genes. The methods and kits of the present invention satisfy the need to classify patients at genetic risk for drug/alcohol seeking behavior prior to or upon entry to residential and or non-residential chemical dependency and pain programs.

1 - 19 . (canceled) 
     
     
         20 . A method of obtaining and utilizing a risk score for evaluating stratification of a plurality of ranges for a genetic addiction risk comprising the steps of:
 (a) obtaining a biological sample from a subject;   (b) performing an allelic analysis on the biological sample to detect the presence of a plurality of pre-determined alleles in the biological sample, wherein
 (i) each of the alleles in the plurality of pre-determined alleles is associated with a gene in a plurality of pre-determined genes, 
 (ii) there are at least ten genes in the plurality of pre-determined genes, 
 (iii) there is at least one allele for each of the genes in the plurality of pre-determined genes, 
 (iv) the plurality of pre-determined alleles comprise at least five alleles in an allele group consisting of
 (A) allele G of gene DRD1; 
 (B) allele A1 of gene DRD2; 
 (C) allele C of gene DRD3; 
 (D) allele C of gene DRD4; 
 (E) allele 9R of gene DAT1; 
 (F) allele 7-11R of gene DRD4; 
 (G) allele S or L of gene HTTLPR; 
 (H) allele 4R of gene MAOA; 
 (I) allele G of gene COMT; 
 (J) allele G of gene OPRM1; and 
 (K) allele 181 of gene GABRB3, and 
 
 (v) the at least five alleles in the allele group comprise
 (A) allele G of gene DRD1; 
 (B) allele A1 of gene DRD2; 
 (G) allele S or L of gene HTTLPR; 
 (I) allele G of gene COMT; and 
 (J) allele G of gene OPRM1; 
 
   (c) assigning a count for each of the alleles in the plurality of pre-determined alleles that was detected to be present in the biological sample, wherein the count for a particular allele is the number of the particular allele detected to be present in the biological sample;   (d) determining a risk score for the subject based upon the count, wherein
 (i) the risk score is the sum of the counts, 
 (ii) stratification of the plurality of ranges of the risk score identifies a severity of the genetic addiction risk of a reward deficiency syndrome behavior, 
 (iii) the risk score in a first pre-determined range for the reward deficiency syndrome behavior identifies a low genetic addiction risk for the subject, and 
 (iv) the risk score in a second pre-determined range for the reward deficiency syndrome behavior identifies a high genetic addiction risk; and 
   (e) administering treatment based upon the severity of the genetic addition risk identified for the subject, wherein, for a high addictive risk identified subject, the treatment comprises treating the subject for the reward deficiency syndrome behavior and further comprises entry of the subject in a residential treatment program for the reward deficiency syndrome behavior of the subject and medically monitoring the reward deficiency syndrome behavior of the subject.   
     
     
         21 . The method of  claim 20 , wherein the plurality of pre-determined alleles comprise at least eight alleles in the allele group. 
     
     
         22 . The method of  claim 20 , wherein
 the genetic addictive risk behavior is for drugs, and   (ii) the second pre-determined range is 4 and above.   
     
     
         23 . The method of  claim 22 , wherein the first predetermined range is from 0 to 1. 
     
     
         24 . The method of  claim 20 , wherein
 (i) the genetic addictive risk behavior is for alcohol, and   (ii) the second pre-determined range is 7 and above.   
     
     
         25 . The method of  claim 24 , wherein the first predetermined range is from 0 to 3. 
     
     
         26 . The method of  claim 20 , wherein the reward deficiency syndrome behavior is selected from the group consisting of addictive behaviors, impulse behaviors, obsessive compulsive behaviors, personality disorder behaviors, and combinations thereof. 
     
     
         27 . The method of  claim 20 , wherein the risk score in a third range for the reward deficiency syndrome behavior identifies a moderate genetic addictive risk. 
     
     
         28 . The method of  claim 20 , wherein
 (i) the genetic addictive risk behavior is for drugs,   (ii) the first pre-determined range is from 0 to 1,   (iii) the second pre-determined range is 4 and above, and   (iv) the third pre-determined range is from 2 to 3.   
     
     
         29 . The method of  claim 20 , wherein
 (i) the genetic addictive risk behavior is for alcohol,   (ii) the first pre-determined range is from 0 to 3,   (iii) the second pre-determined range is 8 and above, and   (iv) the third pre-determined range is from 4 to 7.   
     
     
         30 . The method of  claim 20 , wherein
 (i) the genetic addictive risk behavior is chemical dependency, and   (ii) for a high addictive risk identified subject, the treatment further comprises providing support to reduce the chance of relapse by the diagnosed subject.   
     
     
         31 . The method of  claim 30 , wherein the second pre-determined range is 4 and above. 
     
     
         32 . The method of  claim 30 , wherein, the count for the allele A1 of gene DRD2 is at least one. 
     
     
         33 . A method of obtaining and utilizing a risk score for evaluating stratification of a plurality of ranges for a genetic addiction risk comprising the steps of:
 (a) obtaining a biological sample from a subject;   (b) performing an allelic analysis on the biological sample to detect the presence of a plurality of pre-determined alleles in the biological sample, wherein
 (i) each of the alleles in the plurality of pre-determined alleles is associated with a gene in a plurality of pre-determined genes, 
 (ii) there are at least ten genes in the plurality of pre-determined genes, 
 (iii) there is at least one allele for each of the genes in the plurality of pre-determined genes, 
 (iv) the plurality of pre-determined alleles comprise at least five alleles in an allele group consisting of
 (A) allele G of gene DRD1; 
 (B) allele A1 of gene DRD2; 
 (C) allele C of gene DRD3; 
 (D) allele C of gene DRD4; 
 (E) allele 9R of gene DAT1; 
 (F) allele 7-11R of gene DRD4; 
 (G) allele S or L of gene HTTLPR; 
 (H) allele 4R of gene MAOA; 
 (I) allele G of gene COMT; 
 (J) allele G of gene OPRM1; and 
 (K) allele 181 of gene GABRB3, and 
 
 (v) the at least five alleles in the allele group comprise
 (A) allele G of gene DRD1; 
 (B) allele A1 of gene DRD2; 
 (G) allele S or L of gene HTTLPR; 
 (I) allele G of gene COMT; and 
 (J) allele G of gene OPRM1; 
 
   (c) assigning a count for each of the alleles in the plurality of pre-determined alleles that was detected to be present in the biological sample, wherein the count for a particular allele is the number of the particular allele detected to be present in the biological sample;   (d) determining a risk score for the subject based upon the count, wherein
 (i) the risk score is the sum of the counts, 
 (ii) stratification of the plurality of ranges of the risk score identifies a severity of the genetic addition risk of a reward deficiency syndrome behavior, wherein the reward deficiency syndrome behavior is opioid dependency, 
 (iii) the risk score in a first pre-determined range for the reward deficiency syndrome behavior identifies a low genetic additive risk for the subject, and 
 (iv) the risk score in a second pre-determined range for the reward deficiency syndrome behavior identifies a high genetic additive risk; and 
   (e) administering treatment based upon the severity of the genetic addition risk identified for the subject, wherein, for a high addictive risk identified subject, the treatment comprises providing pain treatment in which the use of opioids is avoided.   
     
     
         34 . The method of  claim 33 , wherein the plurality of pre-determined alleles comprise at least eight alleles in the allele group. 
     
     
         35 . The method of  claim 33 , wherein the pain treatment comprises the use of nonsteroidal anti-inflammatory drugs. 
     
     
         36 . The method of  claim 25 , wherein the second pre-determined range is 4 and above. 
     
     
         37 . A method of obtaining and utilizing a risk score for evaluating stratification of a plurality of ranges for a genetic addiction risk comprising the steps of:
 (a) obtaining a biological sample from a subject;   (b) performing an allelic analysis on the biological sample to detect the presence of a plurality of pre-determined alleles in the biological sample, wherein
 (i) each of the alleles in the plurality of pre-determined alleles is associated with a gene in a plurality of pre-determined genes, 
 (ii) there are at least ten genes in the plurality of pre-determined genes, 
 (iii) there is at least one allele for each of the genes in the plurality of pre-determined genes, and 
 (iv) the plurality of pre-determined alleles comprise at least five alleles in an allele group consisting of
 (A) allele G of gene DRD1; 
 (B) allele A1 of gene DRD2; 
 (C) allele C of gene DRD3; 
 (D) allele C of gene DRD4; 
 (E) allele 9R of gene DAT1; 
 (F) allele 7-11R of gene DRD4; 
 (G) allele S or L of gene HTTLPR; 
 (H) allele 4R of gene MAOA; 
 (I) allele G of gene COMT; 
 (J) allele G of gene OPRM1; and 
 (K) allele 181 of gene GABRB3, and 
 
 (v) the at least five alleles in the allele group comprise
 (A) allele G of gene DRD1; 
 (B) allele A1 of gene DRD2; 
 (G) allele S or L of gene HTTLPR; 
 (I) allele G of gene COMT; and 
 (J) allele G of gene OPRM1; 
 
   (c) assigning a count for each of the alleles in the plurality of pre-determined alleles that was detected to be present in the biological sample, wherein the count for a particular allele is the number of the particular allele detected to be present in the biological sample   (d) determining a risk score for the subject based upon the count, wherein
 (i) the risk score is the sum of the counts, 
 (ii) stratification of the plurality of ranges of the risk score identifies a severity of the genetic addition risk of a reward deficiency syndrome behavior, 
 (iii) the risk score in a first pre-determined range for the reward deficiency syndrome behavior identifies a low genetic additive risk for the subject, and 
 (iv) the risk score in a second pre-determined range for the reward deficiency syndrome behavior identifies a high genetic additive risk; and 
   (e) administering treatment based upon the severity of the genetic addition risk identified for the subject, wherein, for a high addictive risk identified subject, the treatment comprises providing a dopamine regulator.   
     
     
         38 . The method of  claim 37 , wherein the plurality of pre-determined alleles comprise at least eight alleles in the allele group. 
     
     
         39 . The method of  claim 37 , wherein the second pre-determined range is 4 and above. 
     
     
         40 . The method of  claim 37 , wherein, the count for the allele A1 of gene DRD2 is at least one. 
     
     
         41 . The method of  claim 37 , wherein, the count for the allele G of gene OPRM1 is at least one.