Ewa Banach1, Joanna Pawlak2, Pawel Kapelski2, Aleksandra Szczepankiewicz3, Aleksandra Rajewska-Rager2, Maria Skibinska2, Piotr Czerski2, Joanna Twarowska-Hauser2, Monika Dmitrzak-Weglarz2. 1. Psychiatric Genetics Unit, Department of Psychiatry, Poznan University of Medical Sciences, Poland; Laboratory of Neurobiology, Department of Molecular and Cellular Neurobiology, Nencki Institute, Warsaw PL-02-093, Poland. Electronic address: e.banach@nencki.gov.pl. 2. Psychiatric Genetics Unit, Department of Psychiatry, Poznan University of Medical Sciences, Poland. 3. Psychiatric Genetics Unit, Department of Psychiatry, Poznan University of Medical Sciences, Poland; Laboratory of Molecular and Cell Biology, Department of Pulmonology, Pediatric Allergy and Clinical Immunology, Poznan University of Medical Sciences, Poznan, Poland.
Abstract
BACKGROUND: Psychiatric comorbidity affects 24-65% patients with bipolar disorder (BD), 45% of which have alcohol abuse/dependence (AAD). Despite the fact that BD has an equal incidence in both genders, AAD more often occurs in men. We hypothesized that the presence of BD and AAD, reported as a secondary diagnosis, may result from a common genetic background. However, specific genetic factors predispose to gender differences. METHODS: Based on the relationship between circadian clock genes pathway and BD/AAD we decided to test the connection of four core clock genes with common genetic background of both diseases. We analyzed 436 patients with BD, among which 17% were diagnosed with AAD. The control group consisted of 417 healthy subjects. We analyzed 44 SNPs of the previously described core molecular clock genes: CLOCK, ARNTL, TIMELESS and PER3. RESULT: We found association of ARNTL gene (rs11600996) and PER3 gene (rs228642) polymorphisms with an increased risk of BD/AAD in a group of male patients. We also found that two other polymorphisms of PER3 gene, rs228682 and rs2640909, were associated with both AAD and family history of affective disorders. LIMITATIONS: Possible factors that could have influenced the results are: relatively small sample size, gender disproportion and unverifiable data form the patient interview. CONCLUSIONS: Our study confirms the existence of a link between clock genes and increased risk of alcohol abuse/dependence in male patients and the accumulation of risk genes in patients with a positive family history.
BACKGROUND: Psychiatric comorbidity affects 24-65% patients with bipolar disorder (BD), 45% of which have alcohol abuse/dependence (AAD). Despite the fact that BD has an equal incidence in both genders, AAD more often occurs in men. We hypothesized that the presence of BD and AAD, reported as a secondary diagnosis, may result from a common genetic background. However, specific genetic factors predispose to gender differences. METHODS: Based on the relationship between circadian clock genes pathway and BD/AAD we decided to test the connection of four core clock genes with common genetic background of both diseases. We analyzed 436 patients with BD, among which 17% were diagnosed with AAD. The control group consisted of 417 healthy subjects. We analyzed 44 SNPs of the previously described core molecular clock genes: CLOCK, ARNTL, TIMELESS and PER3. RESULT: We found association of ARNTL gene (rs11600996) and PER3 gene (rs228642) polymorphisms with an increased risk of BD/AAD in a group of male patients. We also found that two other polymorphisms of PER3 gene, rs228682 and rs2640909, were associated with both AAD and family history of affective disorders. LIMITATIONS: Possible factors that could have influenced the results are: relatively small sample size, gender disproportion and unverifiable data form the patient interview. CONCLUSIONS: Our study confirms the existence of a link between clock genes and increased risk of alcohol abuse/dependence in male patients and the accumulation of risk genes in patients with a positive family history.
Authors: Nuria de Zavalia; Konrad Schoettner; Jory A Goldsmith; Pavel Solis; Sarah Ferraro; Gabrielle Parent; Shimon Amir Journal: Commun Biol Date: 2021-10-26
Authors: Jake Valeri; Sinead M O'Donovan; Wei Wang; David Sinclair; Ratna Bollavarapu; Barbara Gisabella; Donna Platt; Craig Stockmeier; Harry Pantazopoulos Journal: Front Neurosci Date: 2022-09-07 Impact factor: 5.152