Familial transmission of derived phenotypes for molecular genetic studies of substance use disorders

Abstract

Although family, twin, and adoption studies indicate that genes play a significant etiologic role in the development of substance use disorders (SUDs), detecting specific genes has been difficult due to uncertainties about how to define SUDs, genetic heterogeneity and variable phenotypic expression of SUD genotypes. We used data from families recruited into six contemporaneous studies of children and adults to derive candidate SUD phenotypes using principle factors factor analysis with varimax rotation. We previously found evidence of two SUD phenotypes in offspring: a psychopathology dimension and a cognitive impairment dimension. We found evidence for one SUD-related phenotype in adults that we term Psychopathology and Cognitive Impairment. Parental factor scores significantly predicted both offspring phenotypes, as well as parental SUD (OR=1.41,p<0.001) and offspring SUD (mother's phenotype: OR=1.34,p=0.04; father's phenotype: OR=1.33,p=0.01). Offspring phenotype predicted offspring SUD (psychopathology phenotype: OR=2.96,p<0.001; cognitive impairment: OR=1.33,p=0.04); in offspring, baseline psychopathology predicted SUD at follow-up assessments (OR=1.55,p=0.01). Results suggest that these candidate SUD phenotypes may be useful for genetic studies of SUD.Correspondence: Dr. Stephen V. Faraone, Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, 750 East Adams St., Syracuse, NY 13210; faraones@upstate.edu, 315-464-3113, (315) 464-3255 (fax). Contributors Stephen V. Faraone participated in study design and execution, planned the analyses, and wrote portions of the manuscript Joel J. Adamson performed data analyses and wrote portions of the manuscript Timothy E. Wilens participated in study design and execution and provided clinical comments on the manuscript Michael C. Monuteaux assisted with the statistical analysis. Participated in study design and execution and provided clinical comments on the manuscript Joseph Biederman participated in study design and execution and provided clinical comments on the manuscript Conflict of Interest Dr. Stephen Faraone receives/d research support from, is/has been a speaker for, or is/has been on the advisory board for the following companies: Eli Lilly & Company, McNeil Consumer & Specialty Pharmaceuticals, Shire US Inc., Noven Pharmaceuticals, Cephalon, National Institute of Mental Health (NIMH), National Institute of Child Health and Human Development (NICHHD), and National Institute of Neurological Disorders and Stroke (NINDS). Dr. Timothy Wilens receives/d research support from, is/has been a speaker for, or is/has been on the advisory board for the following Pharmaceutical Companies: Abbott Laboratories, OrthoMcNeil, Eli Lilly and Company, Novartis Pharmaceuticals, Shire Laboratories Inc. and National Institute on Drug Abuse (NIDA). Dr. Joseph Biederman receives/d research support from, is/has been a speaker for, or is/has been on the advisory board for the following Pharmaceutical Companies: Shire, Eli Lilly, Pfizer, McNeil, Ab...

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