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Quantitative Genetic Analysis of Anxiety Trait In Bipolar Disorder
S716
GENETIC VARIANTS AND RISK OF DISEASE Ney Alliey University of Chicago Abstract Background: Different types of genetic variants are associated with risk to develop neuropsychiatric disorders, from CNVs and mutations causing pervasive effect by direct gene disruption to common variants providing modest effect sizes but contributing to polygenic risk in the general population. This educational talk will focus on different methods of analysis and how the risk for some diseases can be calculated using available knowledge. Methods: Risk for disease can be calculated using Bayesian approaches for CNVs and SNPs associated with ASD, Bipolar and Schizophrenia. This is used to illustrate the risks conferred by different types of variants. Results: CNVs are rare events, but carry the largest effect size associated with mental disorders. Mutations in regions like Chromosome 22q11 are associated with a high pleiotropic risk for ASD, SZ or BD, whereas polygenic risk from multiple common variants account for a smaller but widespread risk in the overall population. Conclusions: Usability of these concepts for genetic counseling, genetic tests that are becoming available, including direct-to-consumer tests, and how to take leverage on these resources to plan further studies on different populations will be focused on the discussion.
Abstracts Methods: We studied 619 individuals, 568 participants from 61 extended families and 51 unrelated healthy controls. The sample was 55% female and had a mean age of 43.25 (SD 13.90; range 18–78). Heritability and genetic correlation of the trait scale from the Anxiety State and Trait Inventory (STAI) was computed by using the general linear model (SOLAR package software). Results: We observed that anxiety trait meets the following criteria for an endophenotype of bipolar disorder type I (BPI): 1) association with BPI (individuals with BPI showed the highest trait score (F = 15.20 [5,24], p = 0.009), 2) state-independence confirmed after conducting a test-retest in 321 subjects, 3) co-segregation within families 4) heritability of 0.70 (SE: 0.060), p = 2.33x10-14 and 5) genetic correlation with BPI was 0.20, (SE = 0.17, p = 3.12x10-5). Limitations: Confounding factors such as comorbid disorders and pharmacological treatment could affect the clinical relationship between BPI and anxiety trait. Further research is needed to evaluate if anxiety traits are specially related to BPI in comparison with other traits such as anger, attention or response inhibition deficit, pathological impulsivity or low self-directedness. Conclusions: Anxiety trait is a heritable phenotype that follows a normal distribution when measured not only in subjects with BPI but also in unrelated healthy controls. It could be used as an endophenotype in BPI for the identification of genomic regions with susceptibility genes for this disorder.
Disclosure Nothing to disclose.
Disclosure
http://dx.doi.org/10.1016/j.euroneuro.2017.06.026
Nothing to disclose. http://dx.doi.org/10.1016/j.euroneuro.2017.06.025
QUANTITATIVE GENETIC ANALYSIS OF ANXIETY TRAIT IN BIPOLAR DISORDER
GENE-ENVIRONMENT INTERACTIONS IN RISK FOR DISEASE Consuelo Walss-Bass University of Texas Health Science Center at Houston
Javier Conteras Abstract University of Costa Rica Abstract Background: Bipolar Disorder Type I (BPI) affects approximately 1% of the world population. Although genetic influences on bipolar disorder are well established, identification of genes that predispose to the illness has been difficult. Most genetic studies are based on categorical diagnosis. One strategy to overcome this obstacle is the use of quantitative endophenotypes, as has been done for other medical disorders.
Background: Gene-environment interactions are thought to play a key role in the risk and onset of several psychiatric disorders including schizophrenia, bipolar disorder and depression. Studies have shown association between these disorders and previous exposure to certain stimuli, such as prenatal infection, substance use, childhood trauma, and a dysfunctional family environment. Methods: We will evaluate the latest findings on the combined effects of susceptibility genes and environmental stress on development of mental illness, with a particular focus on vulnerable youth and impact of stressors early in life.
GENETIC VARIANTS AND RISK OF DISEASE Ney Alliey University of Chicago Abstract Background: Different types of genetic variants are associated with risk to develop neuropsychiatric disorders, from CNVs and mutations causing pervasive effect by direct gene disruption to common variants providing modest effect sizes but contributing to polygenic risk in the general population. This educational talk will focus on different methods of analysis and how the risk for some diseases can be calculated using available knowledge. Methods: Risk for disease can be calculated using Bayesian approaches for CNVs and SNPs associated with ASD, Bipolar and Schizophrenia. This is used to illustrate the risks conferred by different types of variants. Results: CNVs are rare events, but carry the largest effect size associated with mental disorders. Mutations in regions like Chromosome 22q11 are associated with a high pleiotropic risk for ASD, SZ or BD, whereas polygenic risk from multiple common variants account for a smaller but widespread risk in the overall population. Conclusions: Usability of these concepts for genetic counseling, genetic tests that are becoming available, including direct-to-consumer tests, and how to take leverage on these resources to plan further studies on different populations will be focused on the discussion.
Abstracts Methods: We studied 619 individuals, 568 participants from 61 extended families and 51 unrelated healthy controls. The sample was 55% female and had a mean age of 43.25 (SD 13.90; range 18–78). Heritability and genetic correlation of the trait scale from the Anxiety State and Trait Inventory (STAI) was computed by using the general linear model (SOLAR package software). Results: We observed that anxiety trait meets the following criteria for an endophenotype of bipolar disorder type I (BPI): 1) association with BPI (individuals with BPI showed the highest trait score (F = 15.20 [5,24], p = 0.009), 2) state-independence confirmed after conducting a test-retest in 321 subjects, 3) co-segregation within families 4) heritability of 0.70 (SE: 0.060), p = 2.33x10-14 and 5) genetic correlation with BPI was 0.20, (SE = 0.17, p = 3.12x10-5). Limitations: Confounding factors such as comorbid disorders and pharmacological treatment could affect the clinical relationship between BPI and anxiety trait. Further research is needed to evaluate if anxiety traits are specially related to BPI in comparison with other traits such as anger, attention or response inhibition deficit, pathological impulsivity or low self-directedness. Conclusions: Anxiety trait is a heritable phenotype that follows a normal distribution when measured not only in subjects with BPI but also in unrelated healthy controls. It could be used as an endophenotype in BPI for the identification of genomic regions with susceptibility genes for this disorder.
Disclosure Nothing to disclose.
Disclosure
http://dx.doi.org/10.1016/j.euroneuro.2017.06.026
Nothing to disclose. http://dx.doi.org/10.1016/j.euroneuro.2017.06.025
QUANTITATIVE GENETIC ANALYSIS OF ANXIETY TRAIT IN BIPOLAR DISORDER
GENE-ENVIRONMENT INTERACTIONS IN RISK FOR DISEASE Consuelo Walss-Bass University of Texas Health Science Center at Houston
Javier Conteras Abstract University of Costa Rica Abstract Background: Bipolar Disorder Type I (BPI) affects approximately 1% of the world population. Although genetic influences on bipolar disorder are well established, identification of genes that predispose to the illness has been difficult. Most genetic studies are based on categorical diagnosis. One strategy to overcome this obstacle is the use of quantitative endophenotypes, as has been done for other medical disorders.
Background: Gene-environment interactions are thought to play a key role in the risk and onset of several psychiatric disorders including schizophrenia, bipolar disorder and depression. Studies have shown association between these disorders and previous exposure to certain stimuli, such as prenatal infection, substance use, childhood trauma, and a dysfunctional family environment. Methods: We will evaluate the latest findings on the combined effects of susceptibility genes and environmental stress on development of mental illness, with a particular focus on vulnerable youth and impact of stressors early in life.