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Causal association of alcohol consumption with bone mineral density in Korean : a mendelian randomization analysis

Other Titles
 멘델리언 무작위배정 분석을 이용한 골밀도와 알코올섭취의 인과성 연구 
 Graduate School of Public Health (보건대학원) 
Issue Date
Background: Bone Mineral Density (BMD) is a diagnostic tool for osteoporosis, which is a systemic bone disease. It is characterized by a decrease in the strength of bone and an increased risk of fracture. With osteoporotic fracture, the quality of life is deteriorated as it causes limitations on routine daily-life, which leads to major problems in health and sometimes results in death. Alcohol consumption is used for prediction of osteoporotic fracture but the impact of alcohol consumption on BMD were reported inconsistently from the observational studies, suggesting that alcohol has negative impact on bone formation directly or indirectly, light drinking is positive on increased bone mass, or alcohol is the secondary factor which may affect on lifestyle so it is not the primary factor of reduced bone mass. Since the impact of alcohol on bone is controversial, our study was designed to reveal the causal association with Mendelian randomization method using genetic variants and eliminating the methodological limitations of observational studies such as residual, uncontrolled confounding, and reverse causality. Materials and Methods: Among the data of Korean Genome and Epidemiology Study (KoGES) cohort conducted in Ansan and Ansung province with over 40 years old from 2001 to 2002, this study included total 8,392 participants who had provided the information of genetic variants, alcohol consumption, and the result of BMD with informed consent. Drinking status and drinking amount were used as exposure variable of alcohol consumption. Polymorphism of rs671 in ALDH2 gene was determined as instrument variable. For outcome variable, T-scores of BMD assessed in Distal radius and Mid-Shaft Tibia with Speed of Sound (SOS) method were used. The causal associations between alcohol consumption and BMDs were tested with two-stage least squares method for Mendelian randomization (MR) analysis. Results: Among 8,392 participants, 4,025 (47.96%) were men and 4,367(52.04%) were women. Current drinker was much higher in men as 71.63% (N=2,883) than in women as 25.28% (N=1,104) and the mean (SD) of drinking amount from current drinkers was 26.86 (31.07) g/day in men and 5.43 (10.86) g/day in women. The effect size (β) of rs671 on drinking amount was confirmed as 7.59 (p <0.001) with the study population and the F-statistics was 281.46. In men, the effect size (β) was 14.54 (p <0.001) with F-statistics= 308.41. For drinking status as exposure, it showed that the number of G allele in rs671 significantly increased the risk of alcohol consumption as OR=2.91 (p <0.001) in all study population and as OR=4.67 (p <0.001) in men and OR=3.03 (p <0.001) in women. According to the result of MR analysis, the current drinker increased DR-BMD by β=0.370 SD (p=0.002) compared to non-current drinker without adjustment, increased by β=0.344 (p=0.003) adjusted for sex and age, and increased by β=0.292 (p=0.012) adjusted for sex, age, diabetes mellitus, medical history, smoking status, and physical activity. In contrast, there was no causal association between drinking status and MST-BMD. The sub-group analysis with men showed similar results as above, while it didn’t suggest any causality with women group in both DR-BMD and MST-BMD. The causal association of drinking amount with BMDs were also analyzed and the result had similar outcomes with drinking status. Conclusion: Considering the causal association between drinking status/drinking amount and DR-BMD, it implies that current drinker has increased DR-BMD so alcohol consumption seems to be beneficial to bone health. Whereas, MST-BMD showed no association and it was also not detected with women’s group at all in both BMDs. Thus, the impact of alcohol on bone health should be interpreted with caution considering the skeletal site and the hormone impact such as estrogen.
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4. Graduate School of Public Health (보건대학원) > Graduate School of Public Health (보건대학원) > 2. Thesis
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