Genetic Determinants of Increased Body Mass Index Partially Mediate the Effect of Elevated Birth Weight on the Increased Risk of Atrial Fibrillation

Background: Although several observational studies have shown an association between birth weight (BW) and atrial fibrillation (AF), controversy remains. In this study, we aimed to explore the role of elevated BW on the etiology of AF.Methods: A two-sample Mendelian randomization (MR) study was designed to infer the causality. The genetic data on the associations of single-nucleotide polymorphisms (SNPs) with BW and AF were separately obtained from two large-scale genome-wide association studies with up to 321,223 and 1,030,836 individuals, respectively. SNPs were identified at a genome-wide significant level (p <5 × 10−8). The inverse variance-weighted (IVW) method was employed to obtain causal estimates as our primary analysis. Sensitivity analyses with various statistical methods were applied to evaluate the robustness of the results, and multivariable MR analysis was conducted to determine whether this association was mediated by the body mass index (BMI).Results: In total, 144 SNPs were identified as the genetic instrumental variables. MR analysis revealed a causal effect of elevated BW on AF (OR = 1.27, 95% CI = 1.14–1.40, p = 5.70 × 10−6). All the results in sensitivity analyses were consistent with the primary result. The effect of BW on AF was attenuated when adjusted for BMI (OR = 1.16, 95% CI = 1.01–1.33, p = 0.04).Conclusions: This study indicated that elevated BW was significantly associated with increased lifelong risk of AF, which may be partially mediated by BMI.

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Causal Association Between Birth Weight and Atrial Fibrillation: Evidence from a Two-Sample Mendelian Randomization Analysis

10.21203/rs.3.rs-36815/v1 ◽

2020 ◽

Author(s):

Songzan Chen ◽

Fangkun Yan ◽

Tian Xu ◽

Yao Wang ◽

Kaijie Zhang ◽

...

Keyword(s):

Atrial Fibrillation ◽

Birth Weight ◽

Mendelian Randomization ◽

Causal Effect ◽

Sensitivity Analyses ◽

P Value ◽

Causal Association ◽

Genome Wide ◽

A Genome ◽

Mr Study

Abstract Background Although several observational studies have shown an association between birth weight (BW) and atrial fibrillation (AF), controversy remains. In this study, we aimed to explore the role of elevated BW on the etiology of AF. Methods A two-sample Mendelian randomization (MR) study was designed to infer the causality. The genetic data on the associations of single nucleotide polymorphisms (SNPs) with BW and AF were separately obtained from two large-scale genome-wide association study with up to 321,223 and 1,030,836 individuals respectively. SNPs were identified at a genome-wide significant level (p-value < 5 × 10− 8). The inverse variance-weighted (IVW) with fixed effects method was performed to obtain causal estimates as our primary analysis. MR-Egger regression was conducted to assess the pleiotropy and sensitivity analyses with various statistical methods were applied to evaluate the robustness of the results. Results In total, 122 SNPs were identified as the genetic instrumental variables. MR analysis revealed a causal effect of elevated BW on AF (OR = 1.21, 95% CI = 1.13–1.29, p-value = 2.39 × 10− 8). The MR-Egger regression suggested no evidence of directional pleiotropy (intercept = 0.00, p-value = 0.62). All the results in sensitivity analyses were consistent with the primary result, which confirmed the causal association between BW and AF. Conclusions The findings from the two-sample MR study indicate a causal effect of elevated BW on AF. This suggests a convenient and effective method to ease the burden of AF by reducing the number of newborns with elevated BW.

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A new genetic locus for antipsychotic-induced weight gain: A genome-wide study of first-episode psychosis patients using amisulpride (from the OPTiMiSE cohort)

Journal of Psychopharmacology ◽

10.1177/0269881120907972 ◽

2020 ◽

Vol 34 (5) ◽

pp. 524-531 ◽

Cited By ~ 1

Author(s):

Sophie E ter Hark ◽

Stéphane Jamain ◽

Dick Schijven ◽

Bochao D Lin ◽

Mark K Bakker ◽

...

Keyword(s):

Body Mass Index ◽

Weight Gain ◽

Body Mass ◽

Association Studies ◽

Genome Wide Association ◽

Chromatin Interaction ◽

First Episode ◽

Genome Wide Association Studies ◽

Genome Wide ◽

A Genome

Background: Antipsychotic-induced weight gain is a common and debilitating side effect of antipsychotics. Although genome-wide association studies of antipsychotic-induced weight gain have been performed, few genome-wide loci have been discovered. Moreover, these genome-wide association studies have included a wide variety of antipsychotic compounds. Aims: We aim to gain more insight in the genomic loci affecting antipsychotic-induced weight gain. Given the variable pharmacological properties of antipsychotics, we hypothesized that targeting a single antipsychotic compound would provide new clues about genomic loci affecting antipsychotic-induced weight gain. Methods: All subjects included for this genome-wide association study ( n=339) were first-episode schizophrenia spectrum disorder patients treated with amisulpride and were minimally medicated (defined as antipsychotic use <2 weeks in the previous year and/or <6 weeks lifetime). Weight gain was defined as the increase in body mass index from before until approximately 1 month after amisulpride treatment. Results: Our genome-wide association analyses for antipsychotic-induced weight gain yielded one genome-wide significant hit (rs78310016; β=1.05; p=3.66 × 10−08; n=206) in a locus not previously associated with antipsychotic-induced weight gain or body mass index. Minor allele carriers had an odds ratio of 3.98 ( p=1.0 × 10−03) for clinically meaningful antipsychotic-induced weight gain (⩾7% of baseline weight). In silico analysis elucidated a chromatin interaction with 3-Hydroxy-3-Methylglutaryl-CoA Synthase 1. In an attempt to replicate single-nucleotide polymorphisms previously associated with antipsychotic-induced weight gain, we found none were associated with amisulpride-induced weight gain. Conclusion: Our findings suggest the involvement of rs78310016 and possibly 3-Hydroxy-3-Methylglutaryl-CoA Synthase 1 in antipsychotic-induced weight gain. In line with the unique binding profile of this atypical antipsychotic, our findings furthermore hint that biological mechanisms underlying amisulpride-induced weight gain differ from antipsychotic-induced weight gain by other atypical antipsychotics.

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Appraising the Causal Association of Plasma Homocysteine Levels With Atrial Fibrillation Risk: A Two-Sample Mendelian Randomization Study

Frontiers in Genetics ◽

10.3389/fgene.2021.619536 ◽

2021 ◽

Vol 12 ◽

Author(s):

Songzan Chen ◽

Fangkun Yang ◽

Tian Xu ◽

Yao Wang ◽

Kaijie Zhang ◽

...

Keyword(s):

Atrial Fibrillation ◽

Genome Wide Association Study ◽

Mendelian Randomization ◽

Plasma Homocysteine ◽

Fixed Effect ◽

Sensitivity Analyses ◽

Causal Association ◽

Genome Wide ◽

A Genome ◽

Increased Risk

BackgroundAlthough several observational studies have suggested an association of elevated plasma homocysteine (Hcy) levels with increased risk of atrial fibrillation (AF), it remains unclear whether this association reflects causality. In this study, we aimed to investigate the causal association of plasma Hcy levels with AF risk.MethodsA two-sample Mendelian randomization (MR) study was designed to investigate the causal association of Hcy with AF. Summary data on association of single nucleotide polymorphisms (SNPs) with Hcy were extracted from the hitherto largest genome-wide association study (GWAS) with up to 44,147 individuals, and statistics data on association of SNPs with AF were obtained from another recently published GWAS with up to 1,030,836 individuals. SNPs were selected at a genome-wide significance threshold (p < 5 × 10–8). Fixed-effect inverse variance weighting (IVW) method was used to calculate the causal estimate. Other statistical methods and leave-one-out analysis were applied in the follow-up sensitivity analyses. MR-Egger intercept test was conducted to detect the potential directional pleiotropy.ResultsIn total, nine SNPs were identified as valid instrumental variables in our two-sample MR analysis. Fixed-effect IVW analysis indicated no evidence of causal association of genetically predicted Hcy with AF. The odds ratio (OR) and 95% confidence interval (CI) of AF per standard deviation (SD) increase in Hcy were 1.077 (0.993, 1.168), p = 0.075. Similar results were observed in the sensitivity analyses. MR-Egger intercept test suggested no evidence of potential horizonal pleiotropy.ConclusionsThis two-sample MR analysis found no evidence to support causal association of Hcy with AF.

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The Association of Obesity and Liver Enzyme Activities in a Student Population at Increased Risk for Cardiovascular Disease / Veza Između Gojaznosti I Aktivnosti Jetrenih Enzima U Studentskoj Populaciji Sa Povećanim Rizikom Za Nastanak Kardiovaskularnih Bolesti

Journal of Medical Biochemistry ◽

10.2478/v10011-012-0024-z ◽

2013 ◽

Vol 32 (1) ◽

pp. 26-31 ◽

Cited By ~ 1

Author(s):

Emina Čolak ◽

Dragana Pap ◽

Nada Majkić-Singh ◽

Ivana Obradović

Keyword(s):

Body Mass Index ◽

Waist Circumference ◽

Liver Enzyme ◽

Body Mass ◽

Statistical Processing ◽

The Body ◽

Control Group ◽

Anthropometric Parameters ◽

Nonalcoholic Fatty Liver ◽

Increased Risk

Summary Background: It has been reported that obesity is associated with metabolic syndrome, insulin resistance, cardiovascular risk but also with nonalcoholic fatty liver disease (NAFLD). The prevalence of obesity in children and adolescents is increasing rapidly all over the world. The aim of this study was to analyze the value of liver enzymes: AST, ALT and γGT in a group of obese students in order to establish their correlation to anthropometric parameters such as: BMI (body mass index), WC (waist circumference), HC (hip circumference), and WHR (waist-to-hip ratio) compared to non-obese students who comprised the control group (CG). Methods: In this study, 238 students from the University of Novi Sad of both sexes (126 men and 112 women) with a mean age of 22.32 ± 1.85 years were included. According to the body mass index (BMI) lower and higher than 25 kg/m2 and waist circumference (WC) lower and higher than 94 cm (80 cm for females) the whole group of 238 students was divided into 2 subgroups: the obese group at increased risk for CVD (Group 1) and the group at lower risk for CVD (Group 2). AST, ALT and γGT activities were determined in fasting blood samples. Results: Statistical processing data revealed significantly higher values of AST, ALT and γGT in the group of students with BMI>25 kg/m2, WC>94 cm for males and WC>80 cm for females, HC>108 cm for males and HC>111 cm for females, and WHR>0.90 for males and WHR>0.80 for females (P<0.001). Significant association was established between anthropometric parameters and liver enzyme levels (P<0.0001). Conclusions: Obese students with higher BMI, WC, HC and WHR values have higher liver enzyme activites and a higher chance to develop NAFLD in the future.

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Nonalcoholic fatty liver disease and the risk of atrial fibrillation stratified by body mass index: a nationwide population-based study

Scientific Reports ◽

10.1038/s41598-021-83367-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

So-Ryoung Lee ◽

Kyung-Do Han ◽

Eue-Keun Choi ◽

Seil Oh ◽

Gregory Y. H. Lip

Keyword(s):

Atrial Fibrillation ◽

Body Mass Index ◽

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Body Mass ◽

Fatty Liver Disease ◽

Nonalcoholic Fatty Liver ◽

Increased Risk ◽

The Impact

AbstractWe evaluated the association between nonalcoholic fatty liver disease (NAFLD) and incident atrial fibrillation (AF) and analyzed the impact of NAFLD on AF risk in relation to body mass index (BMI). A total of 8,048,055 subjects without significant liver disease who were available fatty liver index (FLI) values were included. Subjects were categorized into 3 groups based on FLI: < 30, 30 to < 60, and ≥ 60. During a median 8-year of follow-up, 534,442 subjects were newly diagnosed as AF (8.27 per 1000 person-years). Higher FLI was associated with an increased risk of AF (hazard ratio [HR] 1.053, 95% confidence interval [CI] 1.046–1.060 in 30 ≤ FLI < 60, and HR 1.115, 95% CI 1.106–1.125 in FLI ≥ 60). In underweight subjects (BMI < 18.5 kg/m2), higher FLI raised the risk of AF (by 1.6-fold in 30 ≤ FLI < 60 and by twofold in FLI ≥ 60). In normal- and overweight subjects, higher FLI was associated with an increased risk of AF, but the HRs were attenuated. In obese subjects, higher FLI was not associated with higher risk of AF. NAFLD as assessed by FLI was independently associated with an increased risk of AF in nonobese subjects with BMI < 25 kg/m2. The impact of NAFLD on AF risk was accentuated in lean subjects with underweight.

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Anaesthetic Management of a Super Morbid Obese Patient

Journal of Evidence Based Medicine and Healthcare ◽

10.18410/jebmh/2021/554 ◽

2021 ◽

Vol 8 (32) ◽

pp. 3039-3042

Author(s):

Lekshmi Raj Jalaja ◽

Stuti Lohia ◽

Priyadarsini Bentur ◽

Ravi Ramgiri

Keyword(s):

Body Mass Index ◽

Body Mass ◽

Recovery Period ◽

Well Being ◽

Anaesthetic Management ◽

The Body ◽

World Health ◽

Morbidly Obese ◽

Multisystem Disorder ◽

Increased Risk

‘Obesity’ is defined as a condition with excess body fat to the extent that health and well-being are adversely affected and uses a class system based on the body mass index (BMI), by the world health organization (WHO). Anaesthetic management of morbidly obese is challenging, as there is an increased risk of perioperative respiratory insufficiency and supplemental oxygen must be given throughout recovery period. The incidence of morbid obesity continues to grow and anaesthesiologists are exposed to obese patients presenting for various procedures. The prevalence of obesity is on the upward trend worldwide. Obesity is a multisystem disorder, involving the respiratory and cardiovascular systems, and therefore, undergoing a surgical procedure under anaesthesia may entail a considerable risk. Thus, a multidisciplinary approach is required in treating such patients. Quantification of the extent of obesity is done using the body mass index. BMI is defined as the relationship between weight and height (weight [kg] / height2 [m2 ]).

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Paternal body mass index before conception associated with offspring's birth weight in Chinese population: a prospective study

10.1101/2021.06.17.21258438 ◽

2021 ◽

Author(s):

Renying Xu ◽

Weixiu Zhao ◽

Tao Tan ◽

Haojie Li ◽

Yanping Wan

Keyword(s):

Body Mass Index ◽

Body Weight ◽

Birth Weight ◽

Body Mass ◽

Sensitivity Analyses ◽

Gestational Weight ◽

A Prospective Study ◽

The Relationship ◽

Multivariable Adjustment ◽

Chinese Mother

Whether paternal epigenetic information of nutrition might be inherited by their offspring remained unknown. evaluate the relationship between preconception paternal body weight and their offspring's birth weight in 1,810 Chinese mother-father-baby trios. Information on paternal and maternal preconception body weight and height was collected via a self-reported questionnaire. Birth weight was collected from medical records. Paternal preconception body weight was associated with offspring's birth weight (p trend=0.02) after multivariable adjustment. Each standard deviation increment of paternal body mass index was associated with an additional 29.6 g increase of birth weight (95% confident interval: 5.7g, 53.5g). The association was more pronounced in male neonates, and neonates with overweight mothers, and with mothers who gained excessive gestational weight, compared to their counterparts (all p interaction<0.05). Sensitivity analyses showed similar pattern to that of the main analysis. Paternal preconception body weight was associated with birth weight of their offspring.

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Correlation of Prolonged Total Ischemic Time with Body Mass Index in Kidney Transplant: A Single Center Report

BioScientia Medicina ◽

10.32539/bsm.v5i11.367 ◽

2021 ◽

Vol 5 (11) ◽

pp. 1009-1013

Author(s):

Eriawan Agung Nugroho ◽

Erwin Wibowo ◽

Prathita Amanda Aryani

Keyword(s):

Body Mass Index ◽

Kidney Transplantation ◽

Kidney Transplant ◽

Body Mass ◽

The Body ◽

Health Concern ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Ischemic Time ◽

Increased Risk

Background: Chronic kidney disease (CKD) is a rising health concern worldwide, especially in Indonesia. The treatment of choice for end-stage renal disease is Kidney Transplantation.1 Numerous studies showed that prolonged total ischemic ischemic time may cause hypoxia of the graft tissue and increased risk of ischemia and reperfusion injury (IRI) and delayed graft function (DGF).2 Body mass index of kidney transplant recipients may cause prolonged duration of the procedure, as well as prolonged total ischemic time. This study aimed to determine the correlation between prolonged total ischemic time with body mass index. Method: This was an observational and cross-sectional analysis at Kariadi General Hospital Semarang involving patients who underwent kidney transplantation from January 2016 to December 2019. The total ischemic time was recorded intraoperatively. The Body Mass Index data were provided by medical records. The program used to statistically analyze the data was SPSS 23.0, and Spearman was used for hypothesis testing. Result: This study included 25 kidney transplant recipients. The mean total ischemic time was 43,27 ± 6,63 minutes. There was a significant positive correlation between prolonged ischemic time and body mass index (r= 0,506 ; p= 0,010). Conclusion: Prolonged total ischemic time was positively correlated with increased body mass index and these results are statistically significant.

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Physical activity modifies the risk of atrial fibrillation in obese individuals: The HUNT3 study

European Journal of Preventive Cardiology ◽

10.1177/2047487318784365 ◽

2018 ◽

Vol 25 (15) ◽

pp. 1646-1652 ◽

Cited By ~ 14

Author(s):

Lars E Garnvik ◽

Vegard Malmo ◽

Imre Janszky ◽

Ulrik Wisløff ◽

Jan P Loennechen ◽

...

Keyword(s):

Physical Activity ◽

Atrial Fibrillation ◽

Body Mass Index ◽

Confidence Interval ◽

Body Mass ◽

High Body Mass Index ◽

Overweight And Obesity ◽

Hazard Ratio ◽

Increased Risk

Background Atrial fibrillation is the most common heart rhythm disorder, and high body mass index is a well-established risk factor for atrial fibrillation. The objective of this study was to examine the associations of physical activity and body mass index and risk of atrial fibrillation, and the modifying role of physical activity on the association between body mass index and atrial fibrillation. Design The design was a prospective cohort study. Methods This study followed 43,602 men and women from the HUNT3 study in 2006–2008 until first atrial fibrillation diagnosis or end of follow-up in 2015. Atrial fibrillation diagnoses were collected from hospital registers and validated by medical doctors. Cox proportional hazard regression analysis was performed to assess the association between physical activity, body mass index and atrial fibrillation. Results During a mean follow-up of 8.1 years (352,770 person-years), 1459 cases of atrial fibrillation were detected (4.1 events per 1000 person-years). Increasing levels of physical activity were associated with gradually lower risk of atrial fibrillation ( p trend 0.069). Overweight and obesity were associated with an 18% (hazard ratio 1.18, 95% confidence interval 1.03–1.35) and 59% (hazard ratio 1.59, 95% confidence interval 1.37–1.84) increased risk of atrial fibrillation, respectively. High levels of physical activity attenuated some of the higher atrial fibrillation risk in obese individuals (hazard ratio 1.53, 95% confidence interval 1.03–2.28 in active and 1.96, 95% confidence interval 1.44–2.67 in inactive) compared to normal weight active individuals. Conclusion Overweight and obesity were associated with increased risk of atrial fibrillation. Physical activity offsets some, but not all, atrial fibrillation risk associated with obesity.

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Novel recessive locus for body mass index in childhood asthma

Thorax ◽

10.1136/thoraxjnl-2020-215742 ◽

2021 ◽

pp. thoraxjnl-2020-215742

Author(s):

Sanghun Lee ◽

Jessica Lasky-Su ◽

Sungho Won ◽

Cecelia Laurie ◽

Juan Carlos Celedón ◽

...

Keyword(s):

Body Mass Index ◽

Body Mass ◽

Association Studies ◽

Additive Model ◽

Recessive Model ◽

Genome Wide Association Studies ◽

Association Testing ◽

Genome Wide ◽

Children With Asthma ◽

Recessive Locus

Most genome-wide association studies of obesity and body mass index (BMI) have so far assumed an additive mode of inheritance in their analysis, although association testing supports a recessive effect for some of the established loci, for example, rs1421085 in FTO. In two whole-genome sequencing (WGS) studies of children with asthma and their parents (892 Costa Rican trios and 286 North American trios), we discovered an association between a locus (rs9292139) in LOC102724122 and BMI that reaches genome-wide significance under a recessive model in the combined analysis. As the association does not achieve significance under an additive model, our finding illustrates the benefits of the recessive model in WGS analyses.

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