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Evaluation of the causal effects between subjective wellbeing and cardiometabolic health: mendelian randomisation study.

ABSTRACT: OBJECTIVES:To investigate whether the association between subjective wellbeing (subjective happiness and life satisfaction) and cardiometabolic health is causal. DESIGN:Two sample, bidirectional mendelian randomisation study. SETTING:Genetic data taken from various cohorts comprised of the general population (mostly individuals of European ancestry, plus a small proportion of other ancestries); follow-up analysis included individuals from the United Kingdom. PARTICIPANTS:Summary data were used from previous genome wide association studies (number of participants ranging from 83?198 to 339?224), which investigated traits related to cardiovascular or metabolic health, had the largest sample sizes, and consisted of the most similar populations while minimising sample overlap. A follow-up analysis included 337?112 individuals from the UK Biobank (54% female (n=181?363), mean age 56.87 years (standard deviation 8.00) at recruitment). MAIN OUTCOME MEASURES:Subjective wellbeing and 11 measures of cardiometabolic health (coronary artery disease; myocardial infarction; total, high density lipoprotein, and low density lipoprotein cholesterol; diastolic and systolic blood pressure; body fat; waist to hip ratio; waist circumference; and body mass index). RESULTS:Evidence of a causal effect of body mass index on subjective wellbeing was seen; each 1 kg/m2 increase in body mass index caused a -0.045 (95% confidence interval -0.084 to -0.006, P=0.02) standard deviation reduction in subjective wellbeing. Follow-up analysis of this association in an independent sample from the UK Biobank provided strong evidence of an effect of body mass index on satisfaction with health (?=-0.035 unit decrease in health satisfaction (95% confidence interval -0.043 to -0.027) per standard deviation increase in body mass index, P<0.001). No clear evidence of a causal effect was seen between subjective wellbeing and the other cardiometabolic health measures, in either direction. CONCLUSIONS:These results suggest that a higher body mass index is associated with a lower subjective wellbeing. A follow-up analysis confirmed this finding, suggesting that the effect in middle aged people could be driven by satisfaction with health. Body mass index is a modifiable determinant, and therefore, this study provides further motivation to tackle the obesity epidemic because of the knock-on effects of higher body mass index on subjective wellbeing.

SUBMITTER: Wootton RE

PROVIDER: S-EPMC6155050 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Evaluation of the causal effects between subjective wellbeing and cardiometabolic health: mendelian randomisation study.

Wootton Robyn E RE Lawn Rebecca B RB Millard Louise A C LAC Davies Neil M NM Taylor Amy E AE Munafò Marcus R MR Timpson Nicholas J NJ Davis Oliver S P OSP Davey Smith George G Haworth Claire M A CMA

BMJ (Clinical research ed.) 20180925

<h4>Objectives</h4>To investigate whether the association between subjective wellbeing (subjective happiness and life satisfaction) and cardiometabolic health is causal.<h4>Design</h4>Two sample, bidirectional mendelian randomisation study.<h4>Setting</h4>Genetic data taken from various cohorts comprised of the general population (mostly individuals of European ancestry, plus a small proportion of other ancestries); follow-up analysis included individuals from the United Kingdom.<h4>Participants ...[more]

PMID: 30254091

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Project description:BackgroundThe timing of puberty may have an important impact on adolescent mental health. In particular, earlier age at menarche has been associated with elevated rates of depression in adolescents. Previous research suggests that this relationship may be causal, but replication and an investigation of whether this effect extends to other mental health domains is warranted.MethodsIn this Registered Report, we triangulated evidence from different causal inference methods using a new wave of data (N = 13,398) from the Norwegian Mother, Father, and Child Cohort Study. We combined multiple regression, one- and two-sample Mendelian randomisation (MR), and negative control analyses (using pre-pubertal symptoms as outcomes) to assess the causal links between age at menarche and different domains of adolescent mental health.ResultsOur results supported the hypothesis that earlier age at menarche is associated with elevated depressive symptoms in early adolescence based on multiple regression (β = - 0.11, 95% CI [- 0.12, - 0.09], pone-tailed < 0.01). One-sample MR analyses suggested that this relationship may be causal (β = - 0.07, 95% CI [- 0.13, 0.00], pone-tailed = 0.03), but the effect was small, corresponding to just a 0.06 standard deviation increase in depressive symptoms with each earlier year of menarche. There was also some evidence of a causal relationship with depression diagnoses during adolescence based on one-sample MR (OR = 0.74, 95% CI [0.54, 1.01], pone-tailed = 0.03), corresponding to a 29% increase in the odds of receiving a depression diagnosis with each earlier year of menarche. Negative control and two-sample MR sensitivity analyses were broadly consistent with this pattern of results. Multivariable MR analyses accounting for the genetic overlap between age at menarche and childhood body size provided some evidence of confounding. Meanwhile, we found little consistent evidence of effects on other domains of mental health after accounting for co-occurring depression and other confounding.ConclusionsWe found evidence that age at menarche affected diagnoses of adolescent depression, but not other domains of mental health. Our findings suggest that earlier age at menarche is linked to problems in specific domains rather than adolescent mental health in general.

Project description:A correlation has been reported to exist between exposure factors (e.g. liver function) and acute pancreatitis. However, the specific causal relationship remains unclear. This study aimed to infer the causal relationship between liver function and acute pancreatitis using the Mendelian randomisation method. We employed summary data from a genome-wide association study involving individuals of European ancestry from the UK Biobank and FinnGen. Single-nucleotide polymorphisms (SCNPs), closely associated with liver function, served as instrumental variables. We used five regression models for causality assessment: MR-Egger regression, the random-effect inverse variance weighting method (IVW), the weighted median method (WME), the weighted model, and the simple model. We assessed the heterogeneity of the SNPs using Cochran's Q test. Multi-effect analysis was performed using the intercept term of the MR-Egger method and leave-one-out detection. Odds ratios (ORs) were used to evaluate the causal relationship between liver function and acute pancreatitis risk. A total of 641 SNPs were incorporated as instrumental variables. The MR-IVW method indicated a causal effect of gamma-glutamyltransferase (GGT) on acute pancreatitis (OR = 1.180, 95%CI [confidence interval]: 1.021-1.365, P = 0.025), suggesting that GGT may influence the incidence of acute pancreatitis. Conversely, the results for alkaline phosphatase (ALP) (OR = 0.997, 95%CI: 0.992-1.002, P = 0.197) and aspartate aminotransferase (AST) (OR = 0.939, 95%CI: 0.794-1.111, P = 0.464) did not show a causal effect on acute pancreatitis. Additionally, neither the intercept term nor the zero difference in the MR-Egger regression attained statistical significance (P = 0.257), and there were no observable gene effects. This study suggests that GGT levels are a potential risk factor for acute pancreatitis and may increase the associated risk. In contrast, ALP and AST levels did not affect the risk of acute pancreatitis.

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Evaluation of the causal effects between subjective wellbeing and cardiometabolic health: mendelian randomisation study.

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Evaluation of the causal effects between subjective wellbeing and cardiometabolic health: mendelian randomisation study.

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