Compositions and methods for detecting predisposition to a substance use disorder

Abstract

The present invention provides screening kits, compositions, and diagnostic methods for determining whether a subject has a predisposition to, or likelihood of having, a substance use disorder by determining a nucleic acid methylation profile from a biological sample from the subject, wherein a given profile indicates that the subject has a predisposition to a substance use disorder.

1 . (canceled) 
     
     
         2 . A method of determining whether or not a subject is a user of tobacco, comprising:
 contacting an array with a biological sample from an individual, wherein the array comprises a plurality of probes that amplify at least two loci, wherein each loci comprises at least one CpG dinucleotide whose methylation status is associated with the use of tobacco, wherein the loci are selected from those shown in any of Table 5, Table 9, Table 22, Table 23, Table 25, Table 26, Appendix A, Appendix B, and Appendix C.   
     
     
         3 . The method of  claim 2 , wherein the plurality of probes comprises probes that amplify at least three loci. 
     
     
         4 . The method of  claim 2 , wherein at least a portion of the plurality of probes detect the unmethylated CpG dinucleotide following bisulfite conversion. 
     
     
         5 . The method of  claim 2 , wherein the probes that amplify the at least two loci detect the unmethylated CpG dinucleotide following bisulfite conversion. 
     
     
         6 . The method of  claim 2 , wherein at least a portion of the plurality of probes detect the methylated CpG dinucleotide following bisulfite conversion. 
     
     
         7 . The method of  claim 2 , wherein the probes that amplify the at least two loci detect the methylated CpG dinucleotide following bisulfite conversion. 
     
     
         8 . The method of  claim 2 , wherein the plurality of probes comprises probes that are about 7 nucleotides to about 50 nucleotides in length. 
     
     
         9 . The method of  claim 2 , wherein the plurality of probes comprises probes that are about 10 nucleotides to about 40 nucleotides in length. 
     
     
         10 . The method of  claim 2 , wherein the array is a microarray. 
     
     
         11 . The method of  claim 2 , wherein the at least two loci comprises AHRR and TRPM4. 
     
     
         12 . A method of determining whether or not an individual is dependent on alcohol, comprising:
 contacting an array with a biological sample from an individual, wherein the array comprises a plurality of probes that amplify at least two loci, wherein each loci comprises at least one CpG dinucleotide whose methylation status is associated with alcohol dependence, wherein the loci are selected from those shown in any of Table 6, Table 13, Table 16, Table 17, Table 19, Appendix D, and Appendix E.   
     
     
         13 . The method of  claim 12 , wherein the plurality of probes comprises probes that amplify at least three loci. 
     
     
         14 . The method of  claim 12 , wherein at least a portion of the plurality of probes detect the unmethylated CpG dinucleotide following bisulfite conversion. 
     
     
         15 . The method of  claim 12 , wherein the probes that amplify the at least two loci detect the unmethylated CpG dinucleotide following bisulfite conversion. 
     
     
         16 . The method of  claim 12 , wherein at least a portion of the plurality of probes detect the methylated CpG dinucleotide following bisulfite conversion. 
     
     
         17 . The method of  claim 12 , wherein the probes that amplify the at least two loci detect the methylated CpG dinucleotide following bisulfite conversion. 
     
     
         18 . The method of  claim 12 , wherein the plurality of probes comprises probes that are about 7 nucleotides to about 50 nucleotides in length. 
     
     
         19 . The method of  claim 12 , wherein the plurality of probes comprises probes that are about 10 nucleotides to about 40 nucleotides in length. 
     
     
         20 . The method of  claim 12 , wherein the array is a microarray. 
     
     
         21 . The method of  claim 12 , wherein the at least two loci comprises ABR and CEBPG. 
     
     
         22 . A method of determining whether or not an individual uses nicotine or alcohol, comprising:
 contacting an array with a biological sample from an individual, wherein the array comprises a plurality of probes,
 wherein the plurality of probes comprises probes that amplify at least two loci, each loci comprising at least one CpG dinucleotide whose methylation status is associated with the use of nicotine, wherein the loci are selected from those shown in any of Table 5, Table 9, Table 22, Table 23, Table 25, Table 26, Appendix A, Appendix B, and Appendix C; and 
 wherein the plurality of probes comprises probes that amplify at least two loci, each loci comprising at least one CpG dinucleotide whose methylation status is associated with alcohol dependence, wherein the loci are selected from those shown in any of Table 6, Table 13, Table 16, Table 17, Table 19, Appendix D, and Appendix E. 
   
     
     
         23 . The method of  claim 22 , wherein the plurality of probes comprises probes that amplify at least three loci. 
     
     
         24 . The method of  claim 22 , wherein at least a portion of the plurality of probes detects the unmethylated CpG dinucleotide following bisulfite conversion. 
     
     
         25 . The method of  claim 22 , wherein the probes that amplify the at least two loci detect the unmethylated CpG dinucleotide following bisulfite conversion. 
     
     
         26 . The method of  claim 22 , wherein at least a portion of the plurality of probes detects the methylated CpG dinucleotide following bisulfite conversion. 
     
     
         27 . The method of  claim 22 , wherein the probes that amplify the at least two loci detect the methylated CpG dinucleotide following bisulfite conversion. 
     
     
         28 . The method of  claim 22 , wherein the plurality of probes comprises probes that are about 7 nucleotides to about 50 nucleotides in length. 
     
     
         29 . The method of  claim 22 , wherein the plurality of probes comprises probes that are about 10 nucleotides to about 40 nucleotides in length. 
     
     
         30 . The method of  claim 22 , wherein the array is a microarray. 
     
     
         31 . The method of  claim 22 , wherein the at least two loci comprising at least one CpG dinucleotide whose methylation status is associated with the use of nicotine comprises AHRR and TRPM4, and wherein the at least two loci comprising at least one CpG dinucleotide whose methylation status is associated with alcohol dependence comprises ABR and CEBPG.