Genetic Counseling for Alcohol Use Disorder: Assessment Of Need In Affected And At-Risk Populations

Introduction: Alcohol use disorder (AUD) is highly heritable, yet there has been no investigation regarding the possible benefits of genetic counseling for AUD. This study assessed the beliefs individuals with and at risk for AUD have regarding recurrence risk and etiology of AUD, how the presence of the condition in themselves or their family history has affected their lifestyle decisions, and potential benefit from AUD genetic counseling. Methods: An online questionnaire was distributed through social media to support groups for AUD inviting adults 18 years and older with a personal or family history of AUD. Results: Of the 122 individuals who completed the online questionnaire, 60% of participants perceived a potential benefit of AUD genetic counseling. Participants reported a wide range of estimated recurrence risks for first-degree relatives (5% to 100% for a child; 0% to 80% for a sibling). The most common recurrence risk estimate was 50%. Respondents expressed the most concern for their children developing AUD. Concern level did not influence their perceived benefit of AUD genetic counseling, yet those who felt genetics to be an important cause of AUD were more likely to perceive a benefit from AUD genetic counseling (ρ = .19, df = 120, p = .019). Participants reported many areas of their lives to be affected by AUD. In general participants recognized the multifactorial nature of AUD but seemed to lack a clear understanding of recurrence risk. Discussion:Based on the responses of the participants in the current study, genetic counseling could be beneficial to those with or at risk for AUD. Genetic counseling for this patient population could help clarify recurrence risk misconceptions and facilitate a clearer understanding of the environmental and biological factors that influence the development of AU. Further studies are warranted to evaluate the outcomes of AUD genetic counseling with respect to patient understanding, lifestyle modifications and psychological adaptation. Genetic counselors should be encouraged to reach out to this population

Genetic counseling for alcohol addiction

Though addictions to substances including alcohol are highly heritable, there have been no studies regarding the possible applicability of genetic counseling to this set of conditions. Adults (≥18 years old) with a personal and/or family history of alcohol addiction were recruited to participate in an online survey-based study comprising 43 questions about beliefs/concern about recurrence risk and etiology of alcohol addiction and its impact on childbearing decisions, and perceptions of potential utility of genetic counseling for alcohol addiction. We applied primarily descriptive statistics, but also tested the hypotheses that perceiving genetic counseling to be useful would be associated with: 1) increasing importance attributed to genetics in the etiology of alcohol addiction, and 2) greater concern about recurrence of alcohol addiction (in self and/or children). Overall, the 113 participants recognized the multifactorial nature of alcohol addiction but reported a wide range of estimated recurrence risks for first-degree relatives. Overall, 62% perceived genetic counseling for alcohol addiction to be potentially beneficial. Participants were more likely to perceive a benefit from genetic counseling if they were concerned about recurrence for themselves (p = .021) or perceived genetics to be etiologically important in alcohol addiction (p = .024). Future studies are warranted to evaluate the outcomes of genetic counseling for addictions with respect to patient understanding, lifestyle modifications and psychological adaptation.Medicine, Faculty ofNon UBCMedical Genetics, Department ofPsychiatry, Department ofReviewedFacultyGraduat

Missense Variants in the Histone Acetyltransferase Complex Component Gene TRRAP Cause Autism and Syndromic Intellectual Disability

International audienceAcetylation of the lysine residues in histones and other DNA-binding proteins plays a major role in regulation of eukaryotic gene expression. This process is controlled by histone acetyltransferases (HATs/KATs) found in multiprotein complexes that are recruited to chromatin by the scaffolding subunit transformation/transcription domain-associated protein (TRRAP). TRRAP is evolutionarily conserved and is among the top five genes intolerant to missense variation. Through an international collaboration, 17 distinct de novo or apparently de novo variants were identified in TRRAP in 24 individuals. A strong genotype-phenotype correlation was observed with two distinct clinical spectra. The first is a complex, multi-systemic syndrome associated with various malformations of the brain, heart, kidneys, and genitourinary system and characterized by a wide range of intellectual functioning; a number of affected individuals have intellectual disability (ID) and markedly impaired basic life functions. Individuals with this phenotype had missense variants clustering around the c.3127G>A p.(Ala1043Thr) variant identified in five individuals. The second spectrum manifested with autism spectrum disorder (ASD) and/or ID and epilepsy. Facial dysmorphism was seen in both groups and included upslanted palpebral fissures, epicanthus, telecanthus, a wide nasal bridge and ridge, a broad and smooth philtrum, and a thin upper lip. RNA sequencing analysis of skin fibroblasts derived from affected individuals skin fibroblasts showed significant changes in the expression of several genes implicated in neuronal function and ion transport. Thus, we describe here the clinical spectrum associated with TRRAP pathogenic missense variants, and we suggest a genotype-phenotype correlation useful for clinical evaluation of the pathogenicity of the variants

Missense Variants in the Histone Acetyltransferase Complex Component Gene TRRAP Cause Autism and Syndromic Intellectual Disability.

Acetylation of the lysine residues in histones and other DNA-binding proteins plays a major role in regulation of eukaryotic gene expression. This process is controlled by histone acetyltransferases (HATs/KATs) found in multiprotein complexes that are recruited to chromatin by the scaffolding subunit transformation/transcription domain-associated protein (TRRAP). TRRAP is evolutionarily conserved and is among the top five genes intolerant to missense variation. Through an international collaboration, 17 distinct de novo or apparently de novo variants were identified in TRRAP in 24 individuals. A strong genotype-phenotype correlation was observed with two distinct clinical spectra. The first is a complex, multi-systemic syndrome associated with various malformations of the brain, heart, kidneys, and genitourinary system and characterized by a wide range of intellectual functioning; a number of affected individuals have intellectual disability (ID) and markedly impaired basic life functions. Individuals with this phenotype had missense variants clustering around the c.3127G>A p.(Ala1043Thr) variant identified in five individuals. The second spectrum manifested with autism spectrum disorder (ASD) and/or ID and epilepsy. Facial dysmorphism was seen in both groups and included upslanted palpebral fissures, epicanthus, telecanthus, a wide nasal bridge and ridge, a broad and smooth philtrum, and a thin upper lip. RNA sequencing analysis of skin fibroblasts derived from affected individuals skin fibroblasts showed significant changes in the expression of several genes implicated in neuronal function and ion transport. Thus, we describe here the clinical spectrum associated with TRRAP pathogenic missense variants, and we suggest a genotype-phenotype correlation useful for clinical evaluation of the pathogenicity of the variants