- Chang, Lun-Hsien, Whitfield, John, Liu, Mengzhen, Medland, Sarah, Hickie, Ian, Martin, Nicholas, Verhulst, Brad, Heath, Andrew, Madden, Pamela, Statham, Dixie, Gillespie, Nathan, Gscan Consortium
- Authors: Chang, Lun-Hsien , Whitfield, John , Liu, Mengzhen , Medland, Sarah , Hickie, Ian , Martin, Nicholas , Verhulst, Brad , Heath, Andrew , Madden, Pamela , Statham, Dixie , Gillespie, Nathan , Gscan Consortium
- Date: 2019
- Type: Text , Journal article
- Relation: Drug and Alcohol Dependence Vol. 205, no. (2019), p.
- Full Text: false
- Reviewed:
- Description: Background: Substance use, substance use disorders (SUDs), and psychiatric disorders commonly co-occur. Genetic risk common to these complex traits is an important explanation; however, little is known about how polygenic risk for tobacco or alcohol use overlaps the genetic risk for the comorbid SUDs and psychiatric disorders. Methods: We constructed polygenic risk scores (PRSs) using GWAS meta-analysis summary statistics from a large discovery sample, GWAS & Sequencing Consortium of Alcohol and Nicotine use (GSCAN), for smoking initiation (SI; N = 631,564), age of initiating regular smoking (AI; N = 258,251), cigarettes per day (CPD; N = 258,999), smoking cessation (SC; N = 312,273), and drinks per week (DPW; N = 527,402). We then estimated the fixed effect of these PRSs on the liability to 15 phenotypes related to tobacco and alcohol use, substance use disorders, and psychiatric disorders in an independent target sample of Australian adults. Results: After adjusting for multiple testing, 10 of 75 combinations of discovery and target phenotypes remained significant. PRS-SI (R2 range: 1.98%–5.09 %) was positively associated with SI, DPW, and with DSM-IV and FTND nicotine dependence, and conduct disorder. PRS-AI (R2: 3.91 %) negatively associated with DPW. PRS-CPD (R2: 1.56 %–1.77 %) positively associated with DSM-IV nicotine dependence and conduct disorder. PRS-DPW (R2: 3.39 %–6.26 %) positively associated with only DPW. The variation of DPW was significantly influenced by sex*PRS-SI, sex*PRS-AI and sex*PRS-DPW. Such interaction effect was not detected in the other 14 phenotypes. Conclusions: Polygenic risks associated with tobacco use are also associated with liability to alcohol consumption, nicotine dependence, and conduct disorder. © 2019 Elsevier B.V.
Cohort profile : the Australian genetics of depression study
- Byrne, Enda, Kirk, Katherine, Medland, Sarah, McGrath, John, Colodro-Conde, Lucia, Parker, Richard, Cross, Simone, Sullivan, Lenore, Statham, Dixie, Levinson, Douglas, Licinio, Julio, Wray, Naomi, Hickie, Ian, Martin, Nicholas
- Authors: Byrne, Enda , Kirk, Katherine , Medland, Sarah , McGrath, John , Colodro-Conde, Lucia , Parker, Richard , Cross, Simone , Sullivan, Lenore , Statham, Dixie , Levinson, Douglas , Licinio, Julio , Wray, Naomi , Hickie, Ian , Martin, Nicholas
- Date: 2020
- Type: Text , Journal article
- Relation: BMJ Open Vol. 10, no. 5 (2020), p.
- Full Text:
- Reviewed:
- Description: Purpose Depression is the most common psychiatric disorder and the largest contributor to global disability. The Australian Genetics of Depression study was established to recruit a large cohort of individuals who have been diagnosed with depression at some point in their lifetime. The purpose of establishing this cohort is to investigate genetic and environmental risk factors for depression and response to commonly prescribed antidepressants. Participants A total of 20 689 participants were recruited through the Australian Department of Human Services and a media campaign, 75% of whom were female. The average age of participants was 43 years±15 years. Participants completed an online questionnaire that consisted of a compulsory module that assessed self-reported psychiatric history, clinical depression using the Composite Interview Diagnostic Interview Short Form and experiences of using commonly prescribed antidepressants. Further voluntary modules assessed a wide range of traits of relevance to psychopathology. Participants who reported they were willing to provide a DNA sample (75%) were sent a saliva kit in the mail. Findings to date 95% of participants reported being given a diagnosis of depression by a medical practitioner and 88% met the criteria for a lifetime depressive episode. 68% of the sample report having been diagnosed with another psychiatric disorder in addition to depression. In line with findings from clinical trials, only 33% of the sample report responding well to the first antidepressant they were prescribed. Future plans A number of analyses to investigate the genetic architecture of depression and common comorbidities will be conducted. The cohort will contribute to the global effort to identify genetic variants that increase risk to depression. Furthermore, a thorough investigation of genetic and psychosocial predictors of antidepressant response and side effects is planned. © © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
- Authors: Byrne, Enda , Kirk, Katherine , Medland, Sarah , McGrath, John , Colodro-Conde, Lucia , Parker, Richard , Cross, Simone , Sullivan, Lenore , Statham, Dixie , Levinson, Douglas , Licinio, Julio , Wray, Naomi , Hickie, Ian , Martin, Nicholas
- Date: 2020
- Type: Text , Journal article
- Relation: BMJ Open Vol. 10, no. 5 (2020), p.
- Full Text:
- Reviewed:
- Description: Purpose Depression is the most common psychiatric disorder and the largest contributor to global disability. The Australian Genetics of Depression study was established to recruit a large cohort of individuals who have been diagnosed with depression at some point in their lifetime. The purpose of establishing this cohort is to investigate genetic and environmental risk factors for depression and response to commonly prescribed antidepressants. Participants A total of 20 689 participants were recruited through the Australian Department of Human Services and a media campaign, 75% of whom were female. The average age of participants was 43 years±15 years. Participants completed an online questionnaire that consisted of a compulsory module that assessed self-reported psychiatric history, clinical depression using the Composite Interview Diagnostic Interview Short Form and experiences of using commonly prescribed antidepressants. Further voluntary modules assessed a wide range of traits of relevance to psychopathology. Participants who reported they were willing to provide a DNA sample (75%) were sent a saliva kit in the mail. Findings to date 95% of participants reported being given a diagnosis of depression by a medical practitioner and 88% met the criteria for a lifetime depressive episode. 68% of the sample report having been diagnosed with another psychiatric disorder in addition to depression. In line with findings from clinical trials, only 33% of the sample report responding well to the first antidepressant they were prescribed. Future plans A number of analyses to investigate the genetic architecture of depression and common comorbidities will be conducted. The cohort will contribute to the global effort to identify genetic variants that increase risk to depression. Furthermore, a thorough investigation of genetic and psychosocial predictors of antidepressant response and side effects is planned. © © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
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