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A NOVEL APPROACH TO COMBINE GWAS, PGRS AND GENE-GENE INTERACTIONS IN PSYCHIATRY
Abstracts
S885
substance use and psychiatric disorder. Among them, the most associated were related to immune system and rRNA processing (p-values o 0.001). Besides, within the top 15 differentially expressed genes, most of them were previously associated with mental illness, substance abuse and dependence (for example, CCR3, and CHST7). Discussion: Although, we found an association between emotional disorders and substance abuse, we cannot say whether this is a cause or consequence. The understanding of the biological alterations that trigger the psychiatric disorders and their association with substance abuse, might help to develop prevention strategies to psychiatric disorders and avoid substance abuse. Furthermore, we found no substance abusers with ADHD which may be related with their age (very young individuals). Although we have found no significant co-expression network, we identified 18 pathways as well as 2 biological processes related to immune system, rRNA processing, among others. Therefore, our results suggest that these pathways could be associated with substance abuse in adolescents. It is also worth to mention that our cohort is a very well clinically characterized and unique sample of adolescents with psychiatric disorders and healthy controls, and we are running next year the 3rd year follow up which may increase the sample size of substance abuser and individuals with psychiatric disorders.
Disclosure: Nothing to disclose. http://dx.doi.org/10.1016/j.euroneuro.2017.08.187
using 2-SNP models not included in the polygenic set, not in LD and under weak (β=0.09), intermediate (β=0.15) and strong (β=0.24) interaction strength and C) a combination containing both a polygenic and epistatic component. Five hundred replicates were simulated per condition. We applied C5.0 in an effort to detect these epistatic interactions. C5.0 is a non-parametric algorithm to generate decision tree-based rulesets. Because of its decision tree basis C5.0 only allows for the Boolean operator OR but does allow for non-binary predictors. Each possible combination from the top node to bottom node in the tree is a so-called ruleset and can be used as a predictor in a regression model. Results: We found C5.0 is highly capable of detecting both epistatic SNPs in 100% of the 500 simulations of the strong interaction, 99.2% of the intermediate interaction and 19.2% of the weak interaction models. For the intermediate and weak interactions C5.0 detected only one of the two epistatic SNPs in 0.8% and 41.2% of the replicates. C5.0 was immune to detecting polygenic additivity at the single SNP level. In the polygenic setting of 30% variation explained by an additive effect, C5.0 detected in 11.4% simulations at least one ruleset with no SNP being included more than 13 times Discussion: These results show that C5.0 is able to detect epistasis even in the presence of a phenotype containing strong-single loci and polygenic components. Further work includes creating an R package that embeds these different components through a penalised regression framework to combine all three types of genetic variation (single loci, polygenic components, epistatic components) to better reflect the underlying biology, and to apply this method to cognitive performance in Major Depressive Disorder.
SA116. A NOVEL APPROACH TO COMBINE GWAS, PGRS
AND GENE-GENE INTERACTIONS IN PSYCHIATRY
Disclosure: Nothing to disclose.
n,1
Joeri Meijsen , Alexandros Rammos2, Riccardo Marioni1, Kristin Nicodemus1 1 2
University of Edinburgh Trinity College Dublin
http://dx.doi.org/10.1016/j.euroneuro.2017.08.188
SA117. ATTITUDE OF INDIAN RESEARCH PARTICIPANTS
TOWARDS PRIVACY AND CONFIDENTIALITY
Background: Studies in psychiatric genetics have focused almost solely on single-loci and polygenic associations and have not included possible interactions. Nicodemus et al. (2014, JAMA Psychiatry) introduced a novel statistical model that incorporates single marker, polygenic and epistatic components to assess the association between SNPs in the ZNF804A pathway and cognitive performance in psychosis. Two-SNP interaction modelling was conducted to test for epistasis. This resulted in a regression model that contained the polygenic score and two two-SNP interaction terms, where the epistatic component explained more variation in cognition than the polygenic score. This model is still relatively simplistic in modelling the genetic architecture of complex traits; in particular, the epistatic component, as the model only allowed for pairwise interactions between SNPs. We sought to implement a more flexible specification of the epistatic component by the use of non-parametric rule sets via the algorithm C5.0. Methods: As a proof-of-principle we simulated multiple phenotypes using SNPs located on chromosome 19 explaining A) 30% polygenic variation B) 30% epistatic variation
n
Triptish Bhatia ,1, Nagendra N. Mishra2, Vishwajit L. Nimgaonkar3, Smita N. Deshpande4, Lisa S. Parker3 1
Indo-US Projects, PGIMER, Dr. R.M.L. Hospital L.S. College, Muzaffarpur B.R.A. Bihar University 3 University of Pittsburgh 4 PGIMER, Dr. R.M.L. Hospital 2
Background: The right to privacy—and the related professional duty of confidentiality—allows participants to limit others’ access to information about themselves while still benefiting from healthcare or benefiting others in research. Like the right to give informed consent, the right to privacy and the confidentiality of health information promote wellbeing and protect autonomy or self-determination. This paper reports the first empirical study in India of the beliefs and expectations of patients/participants, their relatives, and IEC members regarding privacy/confidentiality.
S885
substance use and psychiatric disorder. Among them, the most associated were related to immune system and rRNA processing (p-values o 0.001). Besides, within the top 15 differentially expressed genes, most of them were previously associated with mental illness, substance abuse and dependence (for example, CCR3, and CHST7). Discussion: Although, we found an association between emotional disorders and substance abuse, we cannot say whether this is a cause or consequence. The understanding of the biological alterations that trigger the psychiatric disorders and their association with substance abuse, might help to develop prevention strategies to psychiatric disorders and avoid substance abuse. Furthermore, we found no substance abusers with ADHD which may be related with their age (very young individuals). Although we have found no significant co-expression network, we identified 18 pathways as well as 2 biological processes related to immune system, rRNA processing, among others. Therefore, our results suggest that these pathways could be associated with substance abuse in adolescents. It is also worth to mention that our cohort is a very well clinically characterized and unique sample of adolescents with psychiatric disorders and healthy controls, and we are running next year the 3rd year follow up which may increase the sample size of substance abuser and individuals with psychiatric disorders.
Disclosure: Nothing to disclose. http://dx.doi.org/10.1016/j.euroneuro.2017.08.187
using 2-SNP models not included in the polygenic set, not in LD and under weak (β=0.09), intermediate (β=0.15) and strong (β=0.24) interaction strength and C) a combination containing both a polygenic and epistatic component. Five hundred replicates were simulated per condition. We applied C5.0 in an effort to detect these epistatic interactions. C5.0 is a non-parametric algorithm to generate decision tree-based rulesets. Because of its decision tree basis C5.0 only allows for the Boolean operator OR but does allow for non-binary predictors. Each possible combination from the top node to bottom node in the tree is a so-called ruleset and can be used as a predictor in a regression model. Results: We found C5.0 is highly capable of detecting both epistatic SNPs in 100% of the 500 simulations of the strong interaction, 99.2% of the intermediate interaction and 19.2% of the weak interaction models. For the intermediate and weak interactions C5.0 detected only one of the two epistatic SNPs in 0.8% and 41.2% of the replicates. C5.0 was immune to detecting polygenic additivity at the single SNP level. In the polygenic setting of 30% variation explained by an additive effect, C5.0 detected in 11.4% simulations at least one ruleset with no SNP being included more than 13 times Discussion: These results show that C5.0 is able to detect epistasis even in the presence of a phenotype containing strong-single loci and polygenic components. Further work includes creating an R package that embeds these different components through a penalised regression framework to combine all three types of genetic variation (single loci, polygenic components, epistatic components) to better reflect the underlying biology, and to apply this method to cognitive performance in Major Depressive Disorder.
SA116. A NOVEL APPROACH TO COMBINE GWAS, PGRS
AND GENE-GENE INTERACTIONS IN PSYCHIATRY
Disclosure: Nothing to disclose.
n,1
Joeri Meijsen , Alexandros Rammos2, Riccardo Marioni1, Kristin Nicodemus1 1 2
University of Edinburgh Trinity College Dublin
http://dx.doi.org/10.1016/j.euroneuro.2017.08.188
SA117. ATTITUDE OF INDIAN RESEARCH PARTICIPANTS
TOWARDS PRIVACY AND CONFIDENTIALITY
Background: Studies in psychiatric genetics have focused almost solely on single-loci and polygenic associations and have not included possible interactions. Nicodemus et al. (2014, JAMA Psychiatry) introduced a novel statistical model that incorporates single marker, polygenic and epistatic components to assess the association between SNPs in the ZNF804A pathway and cognitive performance in psychosis. Two-SNP interaction modelling was conducted to test for epistasis. This resulted in a regression model that contained the polygenic score and two two-SNP interaction terms, where the epistatic component explained more variation in cognition than the polygenic score. This model is still relatively simplistic in modelling the genetic architecture of complex traits; in particular, the epistatic component, as the model only allowed for pairwise interactions between SNPs. We sought to implement a more flexible specification of the epistatic component by the use of non-parametric rule sets via the algorithm C5.0. Methods: As a proof-of-principle we simulated multiple phenotypes using SNPs located on chromosome 19 explaining A) 30% polygenic variation B) 30% epistatic variation
n
Triptish Bhatia ,1, Nagendra N. Mishra2, Vishwajit L. Nimgaonkar3, Smita N. Deshpande4, Lisa S. Parker3 1
Indo-US Projects, PGIMER, Dr. R.M.L. Hospital L.S. College, Muzaffarpur B.R.A. Bihar University 3 University of Pittsburgh 4 PGIMER, Dr. R.M.L. Hospital 2
Background: The right to privacy—and the related professional duty of confidentiality—allows participants to limit others’ access to information about themselves while still benefiting from healthcare or benefiting others in research. Like the right to give informed consent, the right to privacy and the confidentiality of health information promote wellbeing and protect autonomy or self-determination. This paper reports the first empirical study in India of the beliefs and expectations of patients/participants, their relatives, and IEC members regarding privacy/confidentiality.