The relationship between Body Mass Index (BMI) and several health issues that have an influence on morbidity and mortality has been the focus of research by epidemiologists and scientists with roots in China and the USA. The possibility to further our understanding of the breadth and depth of illnesses connected to obesity exists in the research of the genetic relationship of BMI across a wide variety of prevalent medical problems.

The prevalence of overweightedness and obesity is rising sharply in the United States, and they most certainly make a significant contribution to the burden of chronic health disorders. The incidence rate of osteoarthritis, gallbladder disease, coronary heart disease, high blood pressure, and type 2 diabetes mellitus are the primary end outcomes.

It is highly heritable for variations in body mass index, the parameter used to identify obesity. Type 2 diabetes mellitus (T2DM) and coronary heart disease, which are the leading causes of avoidable morbidity and death, are two chronic illnesses that are closely linked to obesity and severe obesity. Whether obesity is a contributing factor, a confounding factor, or has a shared etiology with these co-occurring illness problems is still up for debate. The results of all metabolic bariatric surgery trials show that the procedure consistently promotes weight reduction, and there is mounting evidence that it also improves mortality rates and has other positive effects on health.

Mendelian randomization: Validating results from research from observational studies

Mendelian randomization examines the association between a risk factor (exposure) and, for instance, a psychiatric condition using genetic variations as a natural experiment (outcome). This method is thought to be proof of a risk factor’s causal effect on a characteristic since it is less susceptible to the effects of confounders between exposure and outcome. Additionally, it enables the association’s directionality to be established.

Correlating BMI indexes with complex illnesses  

In patients with type 2 diabetes, arbitrary pharmacotherapy clinical trials with advanced glucose-lowering drugs, such as SGLT2 inhibitors and GLP-1 receptor agonists, have also demonstrated evidence of weight reduction linked with lowered risk of catastrophic cardiovascular events and treatment with GLP-1 receptor agonists with lifestyle modifications is related with sustained weight loss in obese nondiabetics, but further research is required to examine tolerance and overuse. However, there is a lack of information on how BMI-related illnesses are linked and could be affected by new surgical and pharmaceutical strategies for treating and preventing obesity. Using genetic tools for life-course exposure to BMI, Mendelian randomization (MR) gives estimates of the strength of correlations with illness outcomes, offering a method to look into the potential causative role of BMI in cardiometabolic disease and many other common diseases.

MR analysis within the associated populations

In order to explore the association between BMI and a number of distinct clinical illnesses, genetic risk scores (GRS) based on BMI genetic variations are being used in MR research as genetic tools. Phenome-wide association studies (PheWAS) provide an additional framework for concurrently examining genetic connections across several prevalent illnesses. Although there is substantial and reliable genetic support for the relationship between BMI and a number of the major causes of death, the thorough evaluation of MR associations within a PheWAS in a sizable population may increase our understanding of the range, depth, and interrelatedness of conditions related to obesity.

In addition, this study aims to offer new, compelling evidence for associations between body mass index and risk for a variety of major circulatory system diseases, such as heart failure with restored ejection fraction, atrial fibrillation, aortic valve disease, venous thromboembolism, abdominal aortic aneurysm. These substantial correlations show that excess adiposity has a more widespread effect on cardiovascular disease morbidity than was previously recognized. The MR study also revealed links with a number of other illnesses that are either life-threatening or have a negative impact on quality of life. These included respiratory and genitourinary diseases with a high risk of death, such as chronic renal failure and asthma, as well as illnesses with significant morbidity in the orthopedic and dermatologic systems. Researchers found a restricted number of inverse relationships that are in line with other observational research, such as the relationship between osteoporosis and inguinal hernia.

More than 300 illnesses were included in this research of disease comorbidity networks, and seven communities with considerable intra- and intercommunity linkages of several body mass index-associated disorders were found. The prevalence of skin, renal, pulmonary, eye, and other sensory organ illnesses was increased in certain localities, whereas the prevalence of cardiovascular diseases was increased in others. This broad range of illnesses that have links to genetically influenced BMI adds to the body of research supporting the clinical co-occurrence of several comorbidities brought on by obesity. The results are also in line with a previous study that found that obese diabetic individuals who had metabolic weight reduction surgery saw significant improvements in a number of outcomes.

Globally, the high incidence of obesity has increased. According to the Global Burden of Disease (GBD) report, having a high BMI results in 4 million extra deaths annually, with cardiovascular disease accounting for the majority of these deaths. Twenty illness endpoints were found in the same research using traditional epidemiological investigations, but no MR analysis was used to demonstrate causation. Evidence from the recent SARS-CoV-2 pandemic suggested an increased risk of death in obese COVID-19 patients as well as an elevated risk for severe COVID-19 disease linked with obesity corroborated by two-sample MR studies highlights the urgency of understanding these linkages.

Across rising BMI categories, there observed a startling rise in the load of MR-associated illness codes. Seven communities of diseases with substantial intra- and inter-community links were identified in this study of disease comorbidity networks, which incorporates all highly related disorders from the phenome-wide MR analysis. These findings highlight fresh insights into the complex genetic foundations of obesity and its influence on diseases in the population.


The study oversees a phenome-wide MR study of the relationship between increased BMI and a wide range of conditions accounting for a significant burden of morbidity and mortality in the population. It does this by taking advantage of the breadth of BMI genetic variation and medical disease phenotypes in the Veterans Health Administration electronic health record (EHR).

Article Source: Paper Reference

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Riya Vishwakarma is a consulting content writing intern at CBIRT. Currently, she's pursuing a Master's in Biotechnology from Govt. VYT PG Autonomous College, Chhattisgarh. With a steep inclination towards research, she is techno-savvy with a sound interest in content writing and digital handling. She has dedicated three years as a writer and gained experience in literary writing as well as counting many such years ahead.


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