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World J Med Genet. Dec 27, 2011; 1(1): 4-10
Published online Dec 27, 2011. doi: 10.5496/wjmg.v1.i1.4
Overlap of genetic influences in phenotypes classically categorized as psychiatric vs medical disorders
Richard C McEachin, James D Cavalcoli
Richard C McEachin, James D Cavalcoli, Center for Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI 48109, United States
Author contributions: McEachin RC and Cavalcoli JD collaborated on this work; all authors take responsibility for the contents.
Supported by U54 DA021915, US National Institutes of Health (currently to Cavalcoli JD, and previously to McEachin RC)
Correspondence to: Richard C McEachin, PhD, Research Investigator, Center for Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, United States. mceachin@umich.edu
Telephone: +1-734-9989249 Fax: +1-734-9988571
Received: August 26, 2011
Revised: October 25, 2011
Accepted: December 17, 2011
Published online: December 27, 2011

Psychiatric disorders have traditionally been segregated from medical disorders in terms of drugs, treatment, insurance coverage and training of clinicians. This segregation is consistent with the long-standing observation that there are inherent differences between psychiatric disorders (diseases relating to thoughts, feelings and behavior) and medical disorders (diseases relating to physical processes). However, these differences are growing less distinct as we improve our understanding of the roles of epistasis and pleiotropy in medical genetics. Both psychiatric and medical disorders are predisposed in part by genetic variation, and psychiatric disorders tend to be comorbid with medical disorders. One hypothesis on this interaction posits that certain combinations of genetic variants (epistasis) influence psychiatric disorders due to their impact on the brain, but the associated genes are also expressed in other tissues so the same groups of variants influence medical disorders (pleiotropy). The observation that psychiatric and medical disorders may interact is not novel. Equally, both epistasis and pleiotropy are fundamental concepts in medical genetics. However, we are just beginning to understand how genetic variation can influence both psychiatric and medical disorders. In our recent work, we have discovered gene networks significantly associated with psychiatric and substance use disorders. Invariably, these networks are also significantly associated with medical disorders. Recognizing how genetic variation can influence both psychiatric and medical disorders will help us to understand the etiology of the individual and comorbid disease phenotypes, predict and minimize side effects in drug and other treatments, and help to reduce stigma associated with psychiatric disorders.

Keywords: Epistasis, Genetic pleiotropy, Comorbidity, Mental disorders, Medical disorders