OBJECTIVE: The increasing incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) has led to a gradual increase in MASLD-related hepatocellular carcinomas (HCC). In this context, we aimed to investigate the association between modifiable factors and the risk of incident HCC in patients with MASLD.
METHODS: Two authors independently searched electronic databases (PubMed, Embase, and the Cochrane Library) from their inception to April 1 2023. Observational studies reporting an association between modifiable risk factors and MASLD-related HCC were eligible for inclusion. The effect size on the study outcomes was calculated using a random-effects model and was presented as a risk ratio with 95% confidence interval.
RESULTS: A total of 31 studies covering 1.02 million individuals were included. Regarding lifestyle factors, smoking and alcohol consumption were associated with 30% [1.30 (1.08-1.57)] and 140% [2.41 (1.03-5.65)] risk increase of MASLD-related HCC . Regarding metabolic risk factors, patients with MASLD who were overweight or obese [1.31 (1.13-1.52)], had diabetes [2.08 (1.71-2.53)] and hypertension[1.42 (1.12-1.80)] had a higher risk of developing HCC, while dyslipidemia was negatively associated with MASLD-HCC [0.78 (0.65-0.93)]. The use of metformin, statin and aspirin was associated with 18% [0.82 (0.68-0.98)], 55% [0.45 (0.36-0.56)] and 36% [0.64 (0.44-0.92)] risk reduction in incident HCC, respectively.
CONCLUSIONS: This comprehensive systematic review and meta-analysis showed statistically significant increases in the risk of incident HCC inpatients with MASLD due to smoking, alcohol use, obesity, diabetes and hypertension, whereas metformin, statin and aspirin therapy might modify disease progression.

BACKGROUND: Alzheimer\'s disease (AD) is a progressive neurodegenerative disorder characterized by intricate genetic and environmental etiology. The objective of this study was to identify robust non-genetic risk factors for AD through an updated umbrella review.
METHODS: We conducted a comprehensive search of meta-analyses and systematic reviews on non-genetic risk factors associated with AD in PubMed, Cochrane, Embase, and Ovid Medline up to June 30, 2023. After collecting data, we estimated the summary effect size and their 95% confidence intervals. The degree of heterogeneity between studies was assessed using I2 statistics and a 95% prediction interval was determined. Additionally, we evaluated potential excess significant bias and small study effects within the selected candidate studies.
RESULTS: The umbrella review encompassed a total of 53 eligible papers, which included 84 meta-analyses covering various factors such as lifestyle, diet, environmental exposures, comorbidity or infections, drugs, and biomarkers. Based on the evidence classification criteria employed in this study, two factors as convincing evidence (Class I), including rheumatoid arthritis (RA), potentially reduced the risk of AD, but diabetes significantly increased the risk of AD. Furthermore, three factors as highly suggestive evidence (Class II), namely depression, high homocysteine, and low folic acid level, potentially increased the risk of AD.
CONCLUSIONS: Our findings highlight several risk factors associated with AD that warrant consideration as potential targets for intervention. However, it is crucial to prioritize the identified modifiable risk factors, namely rheumatoid arthritis, diabetes, depression, elevated homocysteine levels, and low folic acid levels to effectively address this complex neurodegenerative disorder.

BACKGROUND: Potentially modifiable risk factors for hepatocellular carcinoma (HCC) have been investigated in observational epidemiology studies in East Asian and European populations, whereas the causal associations of most of these risk factors remain unclear.
METHODS: We collected genome-wide association summary statistics of 22 modifiable risk factors in East Asians and 33 risk factors in Europeans. Genetic summary statistics of HCC were sourced from the Biobank Japan study (1,866 cases and 195,745 controls) for East Asians, and the deCODE genetics study (406 cases and 49,302 controls) and the UK Biobank (168 cases and 372 016 controls) for Europeans. Two-sample Mendelian randomization (MR) analyses were performed independently for East Asian and European populations.
RESULTS: In East Asians, genetically predicted alcohol frequency, ever drinkers, aspartate aminotransferase (AST), hypothyroidism, chronic hepatitis B, and chronic hepatitis C, metabolic dysfunction-associated steatotic liver disease (MASLD), and autoimmune hepatitis were significantly associated with an increased HCC risk (P < 0.05/22). Among European population, alanine transaminase, AST, MASLD, percent liver fat, and liver iron content were significantly associated with a higher risk of HCC (P < 0.05/33). The replication dataset and meta-analysis further confirmed these results.
CONCLUSIONS: Although East Asian and European populations have different factors for HCC, their common modifiable risk factors AST and MASLD for HCC, offer valuable insights for targeted intervention strategies to mitigate society burden of HCC.

BACKGROUND: In the context of the present global aging phenomenon, the senior population and pace of aging in China have emerged as prominent issues on the worldwide stage. Frailty, a complicated condition that is closely linked to the clinical syndrome of advancing age, poses a considerable health risk to older individuals. Frailty status was assessed by the frailty index (FI) ranging from 0 to 1, pre-frailty was defined as >0.10 to <0.25, and frailty was defined as ≥0.25. To look at the connection between modifiable risk factors and frailty progression among individuals in the pre-frailty population.
METHODS: Using pre-frailty patients as characterized by the 32-frailty index, the study focused on middle-aged and elderly persons from China and ultimately recruited 5,411 participants for analysis. The relationship between modifiable factors and changes in pre-frailty status throughout follow-up was investigated. Modifiable factors were body mass index (BMI), abdominal obesity, smoking status, alcohol use, and sleep status. We employed logistic regression to examine the relationships between modifiable risk factors and changes in pre-frailty status, as well as the associations between modifiable factors scores and the corresponding pre-frailty progression. Additionally, we generated the modifiable factors scores and examined how these related to modifications in the pre-frailty stage.
RESULTS: In this study, after a mean follow-up of 6 years, (OR = 0.59, 95%CI: 0.48-0.71) for BMI ≥ 25 kg/m2 and (OR = 0.74, 95%CI: 0.63-0.89) for concomitant abdominal obesity were significantly associated with lower reversal to a healthy state; (OR = 1.24, 95%CI:1.07-1.44) and (OR = 1.25, 95%CI: 1.10-1.42) for the group that negatively progressed further to frailty were significantly associated with increased frailty progression profile. Subsequently, investigation of modifiable factor scores and changes of pre-frailty status found that as scores increased further, frailty developed (OR = 1.12, 95%CI:1.05-1.18), with scores of 3 and 4 of (OR = 1.38, 95%CI: 1.08-1.77) and (OR = 1.52, 95%CI:1.09-2.14). Finally, we also performed a series of stratified analyses and found that rural unmarried men aged 45 to 60 years with less than a high school degree were more likely to develop a frailty state once they developed abdominal obesity.
CONCLUSIONS: In pre-frailty individuals, maintaining more favorable controllable variables considerably enhances the chance of return to normal and, conversely, increase the risk of progressing to the frailty.

BACKGROUND: Informed by the precedent of an American Association of Hip and Knee Surgeons (AAHKS) survey, where 95% of participants reported instigating modifications to preoperative risk factors, this study appraised the approach of Chinese arthroplasty surgeons toward patients who had modifiable risks.
METHODS: An adaptation of the AAHKS survey tool for a Chinese cohort was undertaken. The survey queried 600 Chinese Society of Hip and Knee Surgeons members on whether the perception of unoptimized medical comorbidities and socioeconomic elements affects the propensity to offer surgical procedures.
RESULTS: Out of the distributed surveys, 150 responses were received, culminating in a response rate of 25%. The data illustrate that 98.7% of Chinese surgeons practice restrictions on arthroplasty access for patients who have modifiable risk factors, with notable frequencies for malnutrition (93.3%), anemia (91.3%), recent hyaluronic acid injections (within one month, 88.7%), and corticosteroid injections (within 3 months, 74.7%). Assessment criteria ahead of surgery included limitations such as a body mass index under 40 (47.3%), requirements for smoking cessation (57.3%), an acceptable hemoglobin A1c level (95.3%), and a dependent fasting blood glucose level (88%). Moreover, 87.3% of respondents endorsed the need for additional interventions for certain socioeconomically disadvantaged patients to achieve successful outcomes. A majority of respondents (94.7%) believed that more equitable access to care, facilitated by better-adjusted payment methodologies, could enhance patient outcomes. Current payment schemes were also perceived by a majority to potentially compromise outcomes for patients who have inadequate social support (80.7%), low socioeconomic status (67.3%), and those lacking insurance (72.7%).
CONCLUSIONS: The consistency of the almost 99% response rate in addressing modifiable risk factors prior to arthroplasty aligns closely with the reported practices in the AAHKS survey. These findings underscore the shared valuation of preoperative risk factor optimization by Chinese and American arthroplasty surgeons, notwithstanding divergent healthcare system structures.

UNASSIGNED: Polycystic Ovary Syndrome (PCOS) is a heritable condition with an as yet unclear etiology. Various factors, such as genetics, lifestyle, environment, inflammation, insulin resistance, hyperandrogenism, iron metabolism, and gut microbiota, have been proposed as potential contributors to PCOS. Nevertheless, a systematic assessment of modifiable risk factors and their causal effects on PCOS is lacking. This study aims to establish a comprehensive profile of modifiable risk factors for PCOS by utilizing a two-sample Mendelian Randomization (MR) framework.
UNASSIGNED: After identifying over 400 modifiable risk factors, we employed a two-sample MR approach, including the Inverse Variance Weighted (IVW) method, Weighted Median method, and MR-Egger, to investigate their causal associations with PCOS. The reliability of our estimates underwent rigorous examination through sensitivity analyses, encompassing Cochran\'s Q test, MR-Egger intercept analysis, leave-one-out analysis, and funnel plots.
UNASSIGNED: We discovered that factors such as smoking per day, smoking initiation, body mass index, basal metabolic rate, waist-to-hip ratio, whole body fat mass, trunk fat mass, overall health rating, docosahexaenoic acid (DHA) (22:6n-3) in blood, monounsaturated fatty acids, other polyunsaturated fatty acids apart from 18:2 in blood, omega-3 fatty acids, ratio of bisallylic groups to double bonds, omega-9 and saturated fatty acids, total lipids in medium VLDL, phospholipids in medium VLDL, phospholipids in very large HDL, triglycerides in very large HDL, the genus Oscillibacter, the genus Alistipes, the genus Ruminiclostridium 9, the class Mollicutes, and the phylum Tenericutes, showed a significant effect on heightening genetic susceptibility of PCOS. In contrast, factors including fasting insulin interaction with body mass index, sex hormone-binding globulin, iron, ferritin, SDF1a, college or university degree, years of schooling, household income, the genus Enterorhabdus, the family Bifidobacteriaceae, the order Bifidobacteriales, the class Actinobacteria, and the phylum Actinobacteria were determined to reduce risk of PCOS.
UNASSIGNED: This study innovatively employs the MR method to assess causal relationships between 400 modifiable risk factors and the susceptibility of PCOS risk. It supports causal links between factors like smoking, BMI, and various blood lipid levels and PCOS. These findings offer novel insights into potential strategies for the management and treatment of PCOS.

BACKGROUND: The intricate etiology of autoimmune liver disease (AILD) involves genetic, environmental, and other factors that yet to be completely elucidated. This study comprehensively assessed the causal association between genetically predicted modifiable risk factors and AILD by employing Mendelian randomization.
METHODS: Genetic variants associated with 29 exposure factors were obtained from genome-wide association studies (GWAS). Genetic association data with autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) were also obtained from publicly available GWAS. Univariate and multivariate Mendelian randomization analyses were performed to identify potential risk factors for AILD.
RESULTS: Genetically predicted rheumatoid arthritis (RA) (OR = 1.620, 95%CI 1.423-1.843, P = 2.506 × 10- 13) was significantly associated with an increased risk of AIH. Genetically predicted smoking initiation (OR = 1.637, 95%CI 1.055-2.540, P = 0.028), lower coffee intake (OR = 0.359, 95%CI 0.131-0.985, P = 0.047), cholelithiasis (OR = 1.134, 95%CI 1.023-1.257, P = 0.017) and higher C-reactive protein (CRP) (OR = 1.397, 95%CI 1.094-1.784, P = 0.007) were suggestively associated with an increased risk of AIH. Genetically predicted inflammatory bowel disease (IBD) (OR = 1.212, 95%CI 1.127-1.303, P = 2.015 × 10- 7) and RA (OR = 1.417, 95%CI 1.193-1.683, P = 7.193 × 10- 5) were significantly associated with increased risk of PBC. Genetically predicted smoking initiation (OR = 1.167, 95%CI 1.005-1.355, P = 0.043), systemic lupus erythematosus (SLE) (OR = 1.086, 95%CI 1.017-1.160, P = 0.014) and higher CRP (OR = 1.199, 95%CI 1.019-1.410, P = 0.028) were suggestively associated with an increased risk of PBC. Higher vitamin D3 (OR = 0.741, 95%CI 0.560-0.980, P = 0.036) and calcium (OR = 0.834, 95%CI 0.699-0.995, P = 0.044) levels were suggestive protective factors for PBC. Genetically predicted smoking initiation (OR = 0.630, 95%CI 0.462-0.860, P = 0.004) was suggestively associated with a decreased risk of PSC. Genetically predicted IBD (OR = 1.252, 95%CI 1.164-1.346, P = 1.394 × 10- 9), RA (OR = 1.543, 95%CI 1.279-1.861, P = 5.728 × 10- 6) and lower glycosylated hemoglobin (HbA1c) (OR = 0.268, 95%CI 0.141-0.510, P = 6.172 × 10- 5) were positively associated with an increased risk of PSC.
CONCLUSIONS: Evidence on the causal relationship between 29 genetically predicted modifiable risk factors and the risk of AIH, PBC, and PSC is provided by this study. These findings provide fresh perspectives on the management and prevention strategies for AILD.

In recent years, there has been a rapid increase in the prevalence of benign and malignant tumours of the thyroid gland worldwide, positioning it as one of the most prevalent neoplasms within the endocrine system. While the pathogenesis of thyroid tumours is still unclear, an increasing number of studies have found that certain lifestyle and residence environments are associated with their occurrence and development. This article endeavours to elucidate the correlation between lifestyle, residential environment, and the increased prevalence of thyroid cancer in recent years. It specifies the frequency of the lifestyle and outlines the scope of the residential environment. It also endeavours to summarise the main mechanistic pathways of various modifiable risk factors that cause thyroid cancer. Factors that prevent thyroid cancer include smoking and alcohol consumption, quality and regular sleep, consumption of cruciferous vegetables and dairy products, and consistent long-term exercise. Conversely, individuals with specific genetic mutations have an elevated risk of thyroid cancer from prolonged and frequent use of mobile phones. In addition, individuals who work in high-pressure jobs, work night shifts, and live near volcanoes or in environments associated with pesticides have an elevated risk of developing thyroid cancer. The impact of living near a nuclear power plant on thyroid cancer remains inconclusive. Raising awareness of modifiable risk factors for thyroid cancer will help to accurately prevent and control thyroid cancer. It will provide a scientific basis for future research on lifestyles and living environments suitable for people at high risk of thyroid cancer.

BACKGROUND: Substantial focus has been placed on atrial fibrillation (AF) treatment and associated stroke prevention rather than preventing AF itself. We employed Mendelian randomization (MR) approach to examine the causal relationships between 50 modifiable risk factors (RFs) and AF.
METHODS: Instrumental variables for genetically predicted exposures were derived from corresponding genome-wide association studies (GWASs). Summary-level statistical data for AF were obtained from a GWAS meta-analysis (discovery dataset, N = 1,030,836) and FinnGen (validation dataset, N = 208,594). Univariable and multivariable MR analyses were performed, primarily using inverse variance weighted method with a series of robust sensitivity analyses.
RESULTS: Genetic predisposition to insomnia, daytime naps, apnea, smoking initiation, moderate to vigorous physical activity and obesity traits, including body mass index, waist-hip ratio, central and peripheral fat/fat-free mass, exhibited significant associations with an increased risk of AF. Coffee consumption and ApoB had suggestive increased risks. Hypertension (odds ratio (OR) 95% confidence interval (CI): 5.26 (4.42, 6.24)), heart failure (HF) (OR 95% CI, 4.77 (2.43, 9.37)) and coronary artery disease (CAD) (OR 95% CI: 1.20 (1.16, 1.24)) were strongly associated with AF, while college degree, higher education attachment and HDL levels were associated with a decreased AF risk. Reverse MR found a bidirectional relationship between genetically predicted AF and CAD, HF and ischemic stroke. Multivariable analysis further indicated that obesity-related traits, systolic blood pressure and lower HDL levels independently contributed to the development of AF.
CONCLUSIONS: This study identified several lifestyles and cardiometabolic factors that might be causally related to AF, underscoring the importance of a holistic approach to AF management and prevention.

The risk factors involved in obstructive sleep apnea (OSA) have not been clearly identified yet. We attempted to systematically investigate genetically predicted modifiable risk factors and lifestyle behaviors associated with OSA.
The association between 34 risk factors and OSA was evaluated using the two-sample Mendelian randomization (MR). Genetic variants for risk factors were acquired from European-descent genome-wide studies. Data sources for OSA were extracted from FinnGen study with 16,761 cases and 201,194 controls. The primary analysis chosen was the inverse-variance weighted method.
MR analyses provide evidence of genetically predicted poor overall health rating (odds ratio (OR), 2.82; 95% confidence interval (CI), 1.95-4.08), nap during day (OR, 2.01; 95% CI, 1.37-2.93), high body mass index (BMI) (OR, 1.14; 95% CI, 1.09-1.19), increased body fat mass (OR, 1.83; 95% CI, 1.83-2.05), elevated body water mass (OR, 1.50; 95% CI, 1.31-1.70) and hypertension (OR, 1.81; 95% CI, 1.34-2.45) were associated with higher OSA risk, while high education level (OR, 0.55; 95% CI, 0.40-0.75) correlated with reduced OSA risk. Suggestive evidence was obtained for smoking and waist-to-hip ratio (WHR) with higher OSA odds, and vigorous physical activity, and HDL cholesterol with lower OSA odds. After adjusting for BMI using multivariable MR analysis, the effects of smoking, WHR, vigorous physical activity, and HDL-cholesterol were fully attenuated.
This MR study indicates that overall health rating, nap during day, BMI, body fat mass, body water mass, hypertension, and education are causally associated with the risk of OSA, which means that these modifiable risk factors are key targets for OSA prevention.