Genetic feedback for psychiatric conditions: Where are we now and where are we going

Driver, Morgan N.; Kuo, Sally I‐Chun; Dick, Danielle M.

doi:10.1002/ajmg.b.32815

Cited by 20 publications

(25 citation statements)

References 85 publications

(188 reference statements)

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“…Furthermore, the findings support current counseling practices which addresses physical, societal, material and emotional aspects of individual families [ 47 ]. Our findings also underscore the need to provide contextual information upon delivery of ASD genetic risk information, in line with findings in general psychiatry [ 48 ]. Replication in independent samples is warranted before ethical guidelines relevant to modern genetic testing and counseling in ASD are revised.…”

Section: Discussionsupporting

confidence: 82%

Attitudes among parents of persons with autism spectrum disorder towards information about genetic risk and future health

et al. 2021

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Clinical relevance of genetic testing is increasing in autism spectrum disorder (ASD). Information about genetic risk may contribute to improved diagnostics, treatment and family planning, but may also be perceived as a burden. Knowledge about the families’ preferences with regard to genetic risk information is important for both health care professionals and policy makers. We investigated attitudes towards sharing information about genetic risk of ASD and knowledge about future health among parent members of the Norwegian Autism Association (N = 1455) using a questionnaire, and the relationships with parent and child characteristics, such as age, gender and ASD severity. Most preferred autonomy in deciding whom to inform about genetic risk of ASD (74.4%) and a minority supported extensive intra-familial disclosure of the genetic risk (41.1%). The majority agreed that it is an obligation to know as much as possible relevant for future health (58.0%) and only 51.7% agreed to a principle of a ‘right not to know’. In regression models, the attitudes were associated with opinions about benefits and harms of genetic testing (e.g., treatment, family planning, understanding of ASD pathology, insurance discrimination and family conflict). In sum, the findings show that most parents want to know as much as possible relevant for their children’s future health and keep their autonomy and intra-familial confidentiality about genetic risk information. Nearly half of the parents were not concerned with a “right not to know”. These attitudes can inform development of guidelines and bioethics in the age of genomic precision medicine.

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Section: Discussionsupporting

confidence: 82%

Attitudes among parents of persons with autism spectrum disorder towards information about genetic risk and future health

et al. 2021

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“…Further research is needed to fully understand the potential benefits, and possible harms, of incorporating genetic information (e.g. PGS) into SUD treatment planning (Driver, Kuo, & Dick, 2020 ; Lebowitz, 2019 ; Lebowitz & Ahn, 2018 ).…”

Section: Clinical and Therapeutic Implicationsmentioning

confidence: 99%

Genetics of substance use disorders: a review

Deak

Johnson

2021

Psychol. Med.

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Substance use disorders (SUDs) are prevalent and result in an array of negative consequences. They are influenced by genetic factors (h2 = ~50%). Recent years have brought substantial progress in our understanding of the genetic etiology of SUDs and related traits. The present review covers the current state of the field for SUD genetics, including the epidemiology and genetic epidemiology of SUDs, findings from the first-generation of SUD genome-wide association studies (GWAS), cautions about translating GWAS findings to clinical settings, and suggested prioritizations for the next wave of SUD genetics efforts. Recent advances in SUD genetics have been facilitated by the assembly of large GWAS samples, and the development of state-of-the-art methods modeling the aggregate effect of genome-wide variation. These advances have confirmed that SUDs are highly polygenic with many variants across the genome conferring risk, the vast majority of which are of small effect. Downstream analyses have enabled finer resolution of the genetic architecture of SUDs and revealed insights into their genetic relationship with other psychiatric disorders. Recent efforts have also prioritized a closer examination of GWAS findings that have suggested non-uniform genetic influences across measures of substance use (e.g. consumption) and problematic use (e.g. SUD). Additional highlights from recent SUD GWAS include the robust confirmation of loci in alcohol metabolizing genes (e.g. ADH1B and ALDH2) affecting alcohol-related traits, and loci within the CHRNA5-CHRNA3-CHRNB4 gene cluster influencing nicotine-related traits. Similar successes are expected for cannabis, opioid, and cocaine use disorders as sample sizes approach those assembled for alcohol and nicotine.

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“…While stratifying individuals based upon “polygenic risk” has been shown to aid in mitigating adverse health outcomes related to some health conditions (e.g., coronary disease; 42), similar success has yet to be demonstrated for substance use disorders (SUD). Concerns related to the clinical utility of PGS for substance use outcomes include that current SUD PGS account for a relatively small proportion of variance for clinical phenotypes (~10% at best), misinterpretation of what a PGS means (95% percentile of genetic risk ≠ 95% likelihood of developing disorder), and discrimination of patients based upon genetic information [e.g., 43–45]. Given this context, findings from the current study provide initial evidence that polygenic influences are associated with increased rates of substance use and related problems over the span of important developmental periods ( Figure 2) , periods in which targeted prevention and intervention strategies (e.g., psychoeducation, lifestyle changes) may help circumvent adverse substance-related outcomes later in life.…”

Section: Discussionmentioning

confidence: 99%

Polygenic Scores Predict the Development of Alcohol and Nicotine Use Problems from Adolescence through Young Adulthood

Clark

Deak

2020

Preprint

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ImportanceMolecular genetic studies of alcohol and nicotine use have identified hundreds of genome-wide risk loci. Few studies have examined the influence of aggregate genetic risk on substance use trajectories over time.ObjectiveWe examined the predictive utility of drinking and smoking polygenic risk scores (PRS) for alcohol and nicotine use from late childhood to early adulthood, substance-specific versus broader-liability effects of the respective PRS, and if PRS performance varied between regular consumption versus pathological use.DesignLatent growth curve models with structured residuals were used to assess the predictive utility of drinks per week and regular smoking PRS for measures of alcohol and nicotine consumption and problematic use from age 14 to 34.SettingPRS were generated from the largest discovery sample for alcohol and nicotine use to date (i.e., GSCAN), and examined for associations with alcohol and nicotine use outcomes in the Minnesota Twin Family Study (MTFS).ParticipantsParticipants were members of the MTFS (N=3225), a longitudinal study investigating the development of substance use disorders and related conditions.Main Outcomes and MeasuresOutcomes included alcohol and nicotine use disorder symptoms as defined by the Diagnostic and Statistical Manual of Mental Disorders, measures of alcohol and nicotine consumption (i.e., drinks per occasion, cigarettes per day), and composite variables for alcohol and nicotine use problems.ResultsThe drinks per week PRS was a significant predictor of problematic alcohol use at age 14 and increases in problematic use during young adulthood. The regular smoking PRS was a significant predictor for all nicotine use outcomes. After adjusting for the effects of both PRSs, the regular smoking PRS demonstrated incremental predictive utility for most alcohol use outcomes and remained a significant predictor of nicotine use trajectories.Conclusions and RelevanceHigher PRS for drinks per week and regular smoking were each associated with more problematic levels of substance use over time. Additionally, the regular smoking PRS seems to capture both nicotine-specific and non-specific genetic liability for substance use problems, and may index genetic risk for externalizing behavior in general. Longitudinal PRS prediction approaches may inform personalized substance use intervention approaches.Key PointsQuestionDo polygenic risk scores (PRS) for drinking and smoking predict problematic alcohol and nicotine use from late childhood to early adulthood?FindingsIn the current study, drinks per week and regular smoking PRS generated from the GWAS & Sequencing Consortium of Alcohol and Nicotine use (GSCAN) were associated with higher levels of problematic alcohol and nicotine use assessed longitudinally from ages 14 to 34 in a sample of 3225 individuals.MeaningPolygenic risk scores validated within longitudinal study designs may help inform future substance use intervention and prevention efforts.

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Genetic feedback for psychiatric conditions: Where are we now and where are we going

Cited by 20 publications

References 85 publications

Attitudes among parents of persons with autism spectrum disorder towards information about genetic risk and future health

Attitudes among parents of persons with autism spectrum disorder towards information about genetic risk and future health

Genetics of substance use disorders: a review

Polygenic Scores Predict the Development of Alcohol and Nicotine Use Problems from Adolescence through Young Adulthood

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