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Reviews and Overviews   |    
New Ethical Issues for Genetic Counseling in Common Mental Disorders
Elliot S. Gershon, M.D.; Ney Alliey-Rodriguez, M.D.
Am J Psychiatry 2013;170:968-976. doi:10.1176/appi.ajp.2013.12121558
View Author and Article Information

The authors report no financial relationships with commercial interests.

Supported by NIH grant 1R01MH094483-01A1 to Dr. Gershon and a NARSAD Young Investigator Award to Dr. Alliey-Rodriguez; by the Eklund family; and by the Geraldi Norton Foundation.

From the Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago.

Address correspondence to Dr. Gershon (egershon@yoda.bsd.uchicago.edu).

Copyright © 2013 by the American Psychiatric Association

Received December 13, 2012; Revised March 06, 2013; Accepted March 11, 2013.

Abstract

Objective  Recent genetic findings of high-impact genetic variants in bipolar disorder, schizophrenia, and autism spectrum disorder (ASD) must lead to profound changes in genetic and family counseling. The authors present risk calculations, discuss the ethical implications of these findings, and outline the changes now required in the risk counseling process.

Method  The authors use data from recent mega-analyses and reviews of common and rare risk variants in bipolar disorder, schizophrenia, and ASD to calculate risks of illness based on genetic marker tests. They then consider new ethical issues in mental disorders presented by these risks, including within-family conflicts over genetic testing; effects of genetic discoveries on stigma, abortion, preimplantation procedures, and population screening for susceptibility; and genetic tests as a factor in marital choice.

Results  New structural mutations (de novo copy number variants [CNVs], which are chromosomal microdeletions and microduplications) are present in 4%−7% of patients with bipolar disorder, schizophrenia, or ASD and can occur almost anywhere in the genome. For a person with a de novo CNV, the absolute risk of bipolar disorder, schizophrenia, or ASD is 14%, much higher than the population risk. Rare CNVs have also been identified that are generally not new mutations but constitute very high-effect risk factors, ranging up to 82%.

Conclusions  A substantial minority of patients with bipolar disorder, schizophrenia, and ASD have high-impact detectable genetic events. This greatly changes psychiatric genetic counseling for these patients and families. A psychotherapeutic approach may be needed as a routine part of risk counseling, particularly for resolution of ethical issues and for within-family stigma and conflicts over genetic test results.

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TABLE 1.Rare CNVs: Risks of Illness for Bipolar Disorder, Schizophrenia, and ASDa
Table Footer Note

a ASD=autism spectrum disorder; CNV=copy number variant. Risks of illness are based on Bayesian probabilities. Data are from the comprehensive review of Malhotra and Sebat (22). The criterion for inclusion in this table was association of CNV with illness at p<0.003.

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TABLE 2.De Novo CNVs: Attributable Risk and Risks of Illness for Schizophrenia, Bipolar Disorder, and ASDa
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a ASD=autism spectrum disorder; CNV=copy number variant. Exposed attributable risk is the attributable risk in exposed individuals (i.e., ill individuals who have a de novo CNV), which is the proportion of the ill person’s risk attributable to the CNV.

Table Footer Note

b Based on Bayesian probability. Data are from Xu et al. (24), Malhotra et al. (25), and Sebat et al. (23). Computation of illness risk of any disorder is 1−(1−P1)(1−P2)(1−P3), where Pi is the risk for each disorder. This calculation indirectly accounts for the probability of the occurrence of more than one disorder in any individual as a product of the probability of each diagnosis.

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TABLE 3.Risk of Illness for GWAS-Significant SNP Markers in Bipolar Disorder and Schizophreniaa
Table Footer Note

a GWAS=genome-wide association study; SNP=single-nucleotide polymorphism.

Table Footer Note

b Bipolar disorder data from mega-analysis of the Psychiatric GWAS Consortium Bipolar Disorder Working Group (43) (cases, N=11,977; controls, N=51,672). Schizophrenia data from mega-analysis of Steinberg et al. (44) (cases, N=18,206; controls, N=42,536). Note that for schizophrenia we include only one marker from the major histocompatibility complex (MHC).

Table Footer Note

c Based on Bayesian probability (see the online data supplement).

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