Exploration of the Causal Association Between Behavioral Risk Factors and Gallstone Disease Development in Two European Ancestry Populations

Alyahyawi, Khalid O; Jareebi, Mohammad A; Iskander, Othman A; Othman, Jamaludeen A; Alagsam, Abdulaziz A; Borik, Waseem S; Qaarie, Mohammed Y; Gosadi, Ibrahim M.

doi:10.7759/cureus.37110

Cited by 5 publications

(2 citation statements)

References 25 publications

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“…The study utilized a distinct set of SNPs that are widely used in the literature [15][16][17] for each exposure. Specifically, 80 SNPs for GERD [18], 93 SNPs for smoking initiation [19], six SNPs for smoking intensity [20], seven SNPs for maternal smoking [21], 177 SNPs for vitamin D [22], 65 SNPs for cheese intake [23], 22 SNPs for salad intake [24], three SNPs for coffee intake [25], 79 SNPs for BMI [12], seven SNPs for physical activity [26], and 46, 41, 55, and 89 SNPs for cholesterol, LDL, TG, and HDL, respectively [27].…”

Section: Snp Selectionmentioning

confidence: 99%

Unraveling the Complex Relationship Between Gastroesophageal Reflux Disease, Lifestyle Factors, and Interstitial Lung Disease: Insights From Two-Sample Mendelian Randomization Analyses

Jareebi,

Gharawi,

Shami

et al. 2023

Cureus

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BackgroundAlthough the cause of interstitial lung disease (ILD) remains uncertain, it is believed to be a combination of genetic and non-inherited factors, such as smoking and diet. This research aims to evaluate the impact of gastroesophageal reflux disease (GERD) and other modifiable risk factors on the likelihood of developing ILD by utilizing two-sample Mendelian randomization. MethodologyThe research utilized publicly accessible single-nucleotide polymorphisms (SNPs) that were deemed significant on a genome-wide scale. These SNPs were chosen from prior studies conducted by various consortia. The study examined GERD and a wide range of smoking habits, including the age at which individuals started smoking, the intensity of their smoking, and whether their mothers smoked. Additionally, the study considered other relevant risk factors such as key dietary factors, coffee consumption, body mass index (BMI), and physical activity. The study focused on self-reported ILD as its outcome measure. The genetic information for ILD was sourced from the FinnGen and UK Biobank (UKB) cohorts. ResultsThe study encompassed a wide range of sample sizes, varying from 64,949 to 632,802, for each risk factor collected from multiple consortia. In total, 593 SNPs were included for all risk factors. The findings revealed significant associations between genetically estimated GERD, dietary factors, BMI, and the risk of ILD within the FinnGen consortium. The odds ratios (ORs) indicated an increase in the risk of ILD per unit of GERD (OR = 1.17, p = 0.001), smoking initiation (OR = 1.10, p < 0.05), BMI (OR = 1.15, p = 0.006), and low-density lipoprotein (LDL) (OR = 1.10, p = 0.02). On the other hand, there was a decrease in the risk of ILD per unit increase in coffee intake (OR = 0.64, p = 0.01) and physical activity (OR = 0.79, p=0.03). Additionally, the results demonstrated a significant association between genetically estimated GERD (OR = 1.01, p < 0.05), coffee intake (OR = 1.14, p=0.03), and high-density lipoproteins (HDL) (OR = 1.01, p=0.04) and increased risk of ILD specifically within the UKB. ConclusionsThis research indicates that the development of ILDs may be causally associated with GERD and various factors such as coffee intake, smoking, BMI, physical activity, LDL, and HDL These results hold great importance in terms of devising effective strategies for the treatment and prevention of ILDs.

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Section: Snp Selectionmentioning

confidence: 99%

Unraveling the Complex Relationship Between Gastroesophageal Reflux Disease, Lifestyle Factors, and Interstitial Lung Disease: Insights From Two-Sample Mendelian Randomization Analyses

Jareebi,

Gharawi,

Shami

et al. 2023

Cureus

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“…However, the causal relationship between these risk variables and migraine is sometimes ambiguous and confounding, particularly as cross-sectional data might bias observational research. Mendelian randomization (MR) is a statistical technique that uses genetic variations as instrumental variables to determine the causal effect of an exposure on an outcome [4,5].…”

Section: Introductionmentioning

confidence: 99%

Causal Associations of Modifiable Risk Factors With Migraine: Evidence From Mendelian Randomization Analysis

Jareebi,

Lyall,

Gharawi

et al. 2024

Cureus

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Background and objectives The exact etiology of migraine is unknown; however, it is likely a mixture of genetic and non-genetic factors including lifestyle variables like smoking and diet. This study aims to assess the causal effect of modifiable risk factors on the risk of migraine using two-sample Mendelian randomization. Materials and methods The study used publicly available genome-wide significant single nucleotide polymorphisms (SNPs). The study evaluated a diverse smoking exposure, encompassing age at smoking initiation, smoking intensity, and maternal smoking, alongside other pertinent risk factors, namely key dietary aspects, coffee consumption, BMI, and physical activity. Self-reported migraine was the outcome of the study. The genetic data for migraine were obtained from the FinnGen (Finland) and the UK Biobank (United Kingdom) cohorts. Results With sample sizes ranging from 64,949 to 632,802 for each risk factor collected from several consorts, the study included a total of 282 SNPs for all risk factors. The findings demonstrated that in the FinnGen consortium, genetically estimated dietary factors as well as BMI, were significantly associated with the risk of migraine (OR 0.765 per single unit of BMI, p = 0.011; OR 0.468 per one SD higher cheese intake, p = 0.012; OR 0.286 per one SD higher salad intake, p = 0.004, and 0.625 per one SD higher coffee consumption, p = 0.003, respectively). The results also showed that in the UK Biobank specifically, a genetically estimated history of maternal smoking was significantly associated with an elevated risk of migraine (OR=1.02, p=0.004). Conclusions The latest study implies a connection between maternal smoking and a heightened risk of migraines, whereas cheese intake, salad intake, coffee consumption, BMI, and physical activity are associated with a lower risk of migraine development.

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Novel insights into causal effects of serum lipids and lipid-modifying targets on cholelithiasis

Chen,

Qiu,

Sun

et al. 2023

Gut

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ObjectiveDifferent serum lipids and lipid-modifying targets should affect the risk of cholelithiasis differently, however, whether such effects are causal is still controversial and we aimed to answer this question.DesignWe prospectively estimated the associations of four serum lipids with cholelithiasis in UK Biobank using the Cox proportional hazard model, including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG). Furthermore, we estimated the causal associations of the genetically predicted serum lipids with cholelithiasis in Europeans using the Mendelian randomisation (MR) design. Finally, both drug-target MR and colocalisation analyses were performed to estimate the lipid-modifying targets’ effects on cholelithiasis, includingHMGCR,NPC1L1,PCSK9,APOB, LDLR, ACLY, ANGPTL3, MTTP, PPARA, PPARDandPPARG.ResultsWe found that serum levels of LDL-C and HDL-C were inversely associated with cholelithiasis risk and such associations were linear. However, the serum level of TC was non-linearly associated with cholelithiasis risk where lower TC was associated with higher risk of cholelithiasis, and the serum TG should be in an inverted ‘U-shaped’ relationship with it. The MR analyses supported that lower TC and higher TG levels were two independent causal risk factors. The drug-target MR analysis suggested thatHMGCRinhibition should reduce the risk of cholelithiasis, which was corroborated by colocalisation analysis.ConclusionLower serum TC can causally increase the risk of cholelithiasis. The cholelithiasis risk would increase with the elevation of serum TG but would decrease when exceeding 2.57 mmol/L. The use ofHMGCRinhibitors should prevent its risk.

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Exploration of the Causal Association Between Behavioral Risk Factors and Gallstone Disease Development in Two European Ancestry Populations

Cited by 5 publications

References 25 publications

Unraveling the Complex Relationship Between Gastroesophageal Reflux Disease, Lifestyle Factors, and Interstitial Lung Disease: Insights From Two-Sample Mendelian Randomization Analyses

Unraveling the Complex Relationship Between Gastroesophageal Reflux Disease, Lifestyle Factors, and Interstitial Lung Disease: Insights From Two-Sample Mendelian Randomization Analyses

Causal Associations of Modifiable Risk Factors With Migraine: Evidence From Mendelian Randomization Analysis

Novel insights into causal effects of serum lipids and lipid-modifying targets on cholelithiasis

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