Comparing the utility of homogeneous subtypes of cocaine use and related behaviors with DSM-IV cocaine dependence as traits for genetic association analysis

American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics
Jinbo BiHenry R Kranzler

Abstract

Because DSM-IV cocaine dependence (CD) is heterogeneous, it is not an optimal phenotype to identify genetic variation contributing to risk for cocaine use and related behaviors (CRBs). We used a cluster analytic method to differentiate homogeneous, highly heritable subtypes of CRBs and to compare their utility with that of the DSM-IV CD as traits for genetic association analysis. Clinical features of CRBs and co-occurring disorders were obtained via a poly-diagnostic interview administered to 9,965 participants in genetic studies of substance dependence. A subsample of subjects (N = 3,443) were genotyped for 1,350 single nucleotide polymorphisms (SNPs) selected from 130 candidate genes related to addiction. Cluster analysis of clinical features of the sample yielded five subgroups, two of which were characterized by heavy cocaine use and high heritability: a heavy cocaine use, infrequent intravenous injection group and an early-onset, heavy cocaine use, high comorbidity group. The utility of these traits was compared with the CD diagnosis through association testing of 2,320 affected subjects and 480 cocaine-exposed controls. Analyses examined both single SNP (main) and SNP-SNP interaction (epistatic) effects, separately for Af...Continue Reading

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Citations

Oct 10, 2015·IEEE/ACM Transactions on Computational Biology and Bioinformatics·Jorge González-DomínguezBertil Schmidt
Jun 26, 2015·Alcoholism, Clinical and Experimental Research·Amy B Hart, Henry R Kranzler
Sep 25, 2015·BMC Medical Genomics·Jiangwen SunJinbo Bi
Jan 24, 2018·Neural Plasticity·Lauren M DePoyRyan W Logan
Jan 31, 2019·Translational Psychiatry·Mauricio Arcos-BurgosMaximilian Muenke
Jun 24, 2017·International Journal of Genomics·Ying MengTong Tong Wu
Oct 10, 2020·Psychopharmacology·Vinícius Dokkedal-SilvaMonica Levy Andersen

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