Association between a functional interleukin 6 receptor genetic variant and risk of depression and psychosis in a population-based birth cohort
Year: 2017
Type: article
Study design: Observational Study
Abstract: OBJECTIVE: Interleukin 6 (IL-6) levels are commonly elevated in patients with depression and psychosis and in people who are at risk of developing these disorders. A common, functional variant in the IL6R gene (IL6R Asp358Ala; rs2228145 A > C) is known to dampen down inflammation by impairing IL6R signaling. We have examined the association of Asp358Ala with diagnosis of depression and psychosis, serum IL-6, CRP levels, and a number of risk factors commonly linked with inflammation, depression or psychosis. We predicted that if IL-6 were related to depression/psychosis risk causally, rather than due to confounding, Asp358Ala would be associated with risk of these disorders, serum IL-6, CRP levels, but not with any of the confounders. METHOD: We used data from the population-based ALSPAC birth cohort. Serum IL-6 and CRP levels were measured at age 9 years. Psychotic disorder, ICD-10 diagnosis of severe depressive episode, and total depression score were assessed at age 18 years. IL6R Asp358Ala was genotyped using the Illumina HumanHap550 quad genome-wide SNP genotyping platform. Risk factors assessed include sex, body mass index, social class, ethnicity, maternal education, birth weight, gestational age, maternal post-natal depression, childhood psychological and behavioral problems, and total IQ score. RESULTS: ), consistent with an anti-inflammatory effect downstream of IL-6. Asp358Ala was not associated with total depression score. Asp358Ala was not associated with any of the other risk factors commonly linked with inflammation, depression or psychosis (all P > 0.20). CONCLUSIONS: The findings provide further evidence that the IL-6/IL6R pathways are involved in pathogenesis of severe depression and psychosis, and may be novel therapeutic targets. Previously reported associations between IL-6, depression and psychosis are unlikely to be fully explained by confounding. Based on a small number of cases, findings from the current study need replication in other samples.
Source: Brain Behavior and Immunity
Language: English
Subfield: Biological Psychiatry
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,235
Awards: Genetics and causality: towards more accessible and more reliable Mendelian randomization investigations, G1192034430, G1605161196, NIHR Senior Investigator Award, NIHR Senior Investigator Award, G2292392052, Genetic investigation of life course phenotypes of mental health and illness in the 1946 British birth cohort., Understanding Causes and Developing Effective Interventions For Schizophrenia and Other Psychoses, G3345452146, The Cambridge-UCL Mental Health and Neurosciences Network., G3831911591, Genetic investigation of life course phenotypes of mental health and illness in the 1946 British birth cohort, G4260143917, The Avon Longitudinal Study for Parents and Children: An international resource for population genomic and lifecourse epidemiology. Core programme support 2014-2019., The Avon Longitudinal Study of Parents and Children: An international resource for population
genomics and lifecourse epidemiology. Core Programme Support 2011-2015 and Core programme support 2014-2019, G5562631338, G5570099221, Causal inference in large datasets using genetic instrumental variables: extending Mendelian randomization techniques., MRC Centre for Neuropsychiatric Genetics and Genomics, G5857625837, G6220646397, G6342754709, G6855551814, Inflammation and Immunity in Depression: from novel mechanisms towards therapeutics, Large-scale integrative studies of risk factors in coronary heart disease: from discovery to application (renewal). (Joint funding with MRC), Causal inference in large datasets using genetic instrumental variables: extending Mendelian randomization techniques., The Cambridge-UCL Mental Health and Neurosciences Network., G8256162305, Large-scale integrative studies of risk factors in coronary heart disease: from discovery to application
OpenAlex ID: W2774979768