Pradeep Suri1,2,3,4, Frances M K Williams5, Elizaveta E Elgaeva6,7, Maxim B Freidin5, Olga O Zaytseva8, Yurii S Aulchenko6,9,10, Yakov A Tsepilov6,7. 1. Division of Rehabilitation Care Services, VA Puget Sound Health Care System, Seattle, USA. pradeep.suri@va.gov. 2. Seattle Epidemiologic Research and Information Center, VA Puget Sound Health Care System, S-152-ERIC, 1660 S. Columbian Way, Seattle, WA, 98108, USA. pradeep.suri@va.gov. 3. Department of Rehabilitation Medicine, University of Washington, Seattle, USA. pradeep.suri@va.gov. 4. Clinical Learning, Evidence, and Research (CLEAR) Center, University of Washington, Seattle, USA. pradeep.suri@va.gov. 5. Department of Twin Research and Genetic Epidemiology, School of Life Course Sciences, King's College London, London, UK. 6. Department of Natural Sciences, Novosibirsk State University, Novosibirsk, Russia. 7. Laboratory of Recombination and Segregation Analysis, Institute of Cytology and Genetics, Novosibirsk, Russia. 8. Genos Glycoscience Research Laboratory, 10000, Zagreb, Croatia. 9. PolyOmica, 's-Hertogenbosch, The Netherlands. 10. Kurchatov Genomics Center, Institute of Cytology & Genetics, Novosibirsk, Russia.
Abstract
PURPOSE: Risk factors for chronic back pain (CBP) may share underlying genetic factors, making them difficult to study using conventional methods. We conducted a bi-directional Mendelian randomisation (MR) study to examine the causal effects of risk factors (education, smoking, alcohol consumption, physical activity, sleep and depression) on CBP and the causal effect of CBP on the same risk factors. METHODS: Genetic instruments for risk factors and CBP were obtained from the largest published genome-wide association studies (GWAS) of risk factor traits conducted in individuals of European ancestry. We used inverse weighted variance meta-analysis (IVW), Causal Analysis Using Summary Effect (CAUSE) and sensitivity analyses to examine evidence for causal associations. We interpreted exposure-outcome associations as being consistent with a causal relationship if results with IVW or CAUSE were statistically significant after accounting for multiple statistical testing (p < 0.003), and the direction and magnitude of effect estimates were concordant between IVW, CAUSE, and sensitivity analyses. RESULTS: We found evidence for statistically significant causal associations between greater education (OR per 4.2 years of schooling = 0.54), ever smoking (OR = 1.27), greater alcohol consumption (OR = 1.29 per consumption category increase) and major depressive disorder (OR = 1.41) and risk of CBP. Conversely, we found evidence for significant causal associations between CBP and greater alcohol consumption (OR = 1.19) and between CBP and smoking (OR = 1.21). Other relationships did not meet our pre-defined criteria for causal association. CONCLUSION: Fewer years of schooling, smoking, greater alcohol consumption, and major depressive disorder increase the risk of CBP. CBP increases the risk of greater alcohol consumption and smoking.
PURPOSE: Risk factors for chronic back pain (CBP) may share underlying genetic factors, making them difficult to study using conventional methods. We conducted a bi-directional Mendelian randomisation (MR) study to examine the causal effects of risk factors (education, smoking, alcohol consumption, physical activity, sleep and depression) on CBP and the causal effect of CBP on the same risk factors. METHODS: Genetic instruments for risk factors and CBP were obtained from the largest published genome-wide association studies (GWAS) of risk factor traits conducted in individuals of European ancestry. We used inverse weighted variance meta-analysis (IVW), Causal Analysis Using Summary Effect (CAUSE) and sensitivity analyses to examine evidence for causal associations. We interpreted exposure-outcome associations as being consistent with a causal relationship if results with IVW or CAUSE were statistically significant after accounting for multiple statistical testing (p < 0.003), and the direction and magnitude of effect estimates were concordant between IVW, CAUSE, and sensitivity analyses. RESULTS: We found evidence for statistically significant causal associations between greater education (OR per 4.2 years of schooling = 0.54), ever smoking (OR = 1.27), greater alcohol consumption (OR = 1.29 per consumption category increase) and major depressive disorder (OR = 1.41) and risk of CBP. Conversely, we found evidence for significant causal associations between CBP and greater alcohol consumption (OR = 1.19) and between CBP and smoking (OR = 1.21). Other relationships did not meet our pre-defined criteria for causal association. CONCLUSION: Fewer years of schooling, smoking, greater alcohol consumption, and major depressive disorder increase the risk of CBP. CBP increases the risk of greater alcohol consumption and smoking.
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Authors: Frances M K Williams; Aruna T Bansal; Joyce B van Meurs; Jordana T Bell; Ingrid Meulenbelt; Pradeep Suri; Fernando Rivadeneira; Philip N Sambrook; Albert Hofman; Sita Bierma-Zeinstra; Cristina Menni; Margreet Kloppenburg; P Eline Slagboom; David J Hunter; Alex J MacGregor; Andre G Uitterlinden; Tim D Spector Journal: Ann Rheum Dis Date: 2012-09-19 Impact factor: 19.103
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