Gwas OCD and Genes Essay

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Personal Details of Student

Family Name: Rooney

Given Name (s) Bridget

Student Number (SID): 312165250

Email (University email only) [email protected]

GWAS OCD

Assignment number (if applicable): #1

Becker

Genetics of Brian and Mind Disorders

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Date: 10 / 09 / 15 Bridget L. Rooney

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Introduction

Anxiety is unlike fear in that it is a long-lasting response to danger signals that proceed beyond actual risk or out of proportion to the possibility of a threat. It is an intense reaction that affect individuals tremendously, severely impacting their day-to-day lives. An example of an anxiety disorder subtype as defined by the DSM-IV is Obsessive-Compulsive Disorder (OCD). In the continued effort to understand and treat OCD, there is emerging research that suggests a genetic and hereditary component to the disorder.

This is a disorder with symptoms including a complex combination of intrusive obsessions and highly ritualized compulsions. OCD is a relatively frequently diagnosed neuropsychiatric disorder. Theoretically, OCD encompasses both the compulsions and obsessions leading to the entire range of behaviours and unique human thoughts that affect individuals. (Geller, et al. 2003). According to Mattheisen et al. (2014), the disorder is "characterized by intrusive thoughts and urges and repetitive, intentional behaviors that cause significant distress and impair functioning." These intrusive thoughts often cause individuals to obsess over otherwise seemingly trivial issues or concerns and feel the need to ritualize their lives in order to keep a certain balance (Knopp et al., 2013). Those who suffer from OCD often express repetitive, compulsive behaviors that are thought to be based from an internal feeling of a loss of control (Burguirer et al., 2015). Many of the disruptive thoughts or need for rituals have been attributed to neurological abnormalities, such as the "disrupted neurotransmission of glutamate within corticostriatal-thalamocortical circuitry" (Davis et al., 2013). Several other studies have also shown abnormal neurological functioning as a primary causation for OCD expression (Ahmari et al., 2013). Murphy et al. (2013) also show that those suffering from OCD tend to exhibit symptoms of other psychological disorders as well. According to the study, over 70% of individuals with OCD have major depressive disorder, with another 10% of individuals also having bipolar disorder (Murphy et al., 2013). OCD expression is often seen with disorders such as Tourette Syndrome as well, which is also thought to have a genetic component that allows families to pass on the disorder to children (Sachdev et al., 2012). According to Murphy et al. (2013), "OCD resembles disorders such as depression, in which gene x gene interactions, gene x environment interactions and stress elements coalesce to yield OC symptoms and, in some individuals, full-blown OCD with multiple comorbid disorders." Thus, there is a connection between other psychological stresses that have also been connected with genetic inheritance.

Research on OCD has uncovered some hereditary connects in regards to individuals exhibiting symptoms associated with the disorder. Studies have shown particular gene markers that are thought to contribute to the pathobiology of OCD (Browne et al., 2014). According to Stewart et al.'s 2013 report, "Genome-wide association study of obsessive compulsive disorder," OCD is a common, debilitating neuropsychiatric illness with complex genetic etiology.

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" A number of family-designs and twin studies have been shown to suggest there is a component of heredity that is associated with the etiology of OCD (Arnold et al., 2006). Specifically, genetic variance account for 40% of compulsive and obsessive behaviours for the sampled twin studies (Stein, Andersen, & Overo, 2007) (Zohar, Greenberg, & Denys, 2012). Familial association studies have suggested first-degree relatives of individuals affected with OCD are two times more likely to develop the disorder as an adult compared to the rest of the population, which was represented through using first-degree relatives of unaffected control subjects (Pauls et al., 2014). Additionally Mattheisen at al. (2014) conducted a similar study on 1,065 families, totaling a sample of over 5,000 individuals. Through SNP analysis testing, the study found markers along chromosome 9, where "pre-synaptic PTPRD promotes the differentiation of glutamatergic synapses and interacts with SLITRK" (Mattheisen et al., 2014). Although no significant SNPs were exactly correlated with the presence of OCD directly, the study did show significant enrichment in certain SNP characteristics at particular chromosome markers. Thus, prior research has made clear connections with genetic heredity and the expression of OCD symptoms and behaviors within genetically linked familial groups.

A number of studies have found genetic architectural variations in key parts of the brain as being associated with the presence of OCD. Murphy et al. (2013) concluded that common genetic variants included issues with the serotonin transporter gene (S:C6A4), "the brain-derived neurotrophic factor (BDNF) gene, and rare variants in genes / chromosomal abnormalities." Another study conducted by Davis et al. (2013) found clear genetic architectures that were distinct in the expression of OCD, mainly abnormal gene expression in the parietal cortex and cerebellum. Representatively, examining hereditary gene characteristics reveals a genetic component to OCD, but that it is not the only factor that contributes to its condition (Moran, 2013).

In addition to genetic factors, there have been clearly outlined environmental factors that greatly increase an individual's likelihood of expressing OCD symptoms (Gorenstein et al., 2015). Heredity has been identified as one of the major causes of the OCD transmitted within families; yet at the same time genetic heredity does not explain the entire picture. Additional research has also linked OCD transmission within families due to a shared environment factors (Ruscio et al., 2010). In addition to possible genetic heritage links, OCD behavior can be picked up through observation of compulsive-obsessive symptoms within family members. (Pauls et al., 2014). Since there is such a high number of individuals with OCD that also have depressive disorders, one can assume a genetic link attached to both disorders that can be carried through family heritage, but also augmented with external environmental factors. Moreover, non-shared environmental factors contribute to 51% of the OCD (Stein, Andersen, & Overo, 2007) (Mattheisen et al., 2014).

However, prior research has failed to show a significant connection between genetic and environmental factors that can be seen as best identifying risks for OCD. Stewart et al. (2013) conducted a study which found no SNPs directly significant in the presence of OCD, there were additional findings of "enrichment of methylation QTLs and frontal lobe expression quantitative trait loci" that was seen within the highest ranking SNPs in the control analysis. Prior research has uncovered some signs of a correlation, but more research is needed to really clarify the level of significance between the hereditary of SNP characteristics and the later expression of OCD behaviors within familial groups.

Methodology

Thus, this current research is an attempt to develop better models in order to blend genetic and environmental stimuli observations in order to portray a more multi-faceted explanation for the presence of OCD. The study focuses on the use of the Genome-Wide Association Studies (GWAS) to identify potential genetic regions of interest, which can better explore the potential genetic source of OCD behaviors (Stewart and Pauls, 2010). This can then serve as a basis for providing data for studies attempting to explore both a genetic link and a combined connection between genetic and environmental factors. The objective for this lab-report was to used statistical and computational tools to analyze the GWAS to deliver an effective method for understanding novel strategies to address OCD obstacles.

Study Exclusion/Inclusion

The study selects all subjects from European ancestry to address the problem of overrepresentation of variance that occurs across ethnic groups. If the study was to mix the.....

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