scholarly journals Systemic evaluation of the relationship between psoriasis, psoriatic arthritis and osteoporosis: observational and Mendelian randomisation study

2020 ◽  
Vol 79 (11) ◽  
pp. 1460-1467 ◽  
Author(s):  
Jiangwei Xia ◽  
Shu-Yang Xie ◽  
Ke-Qi Liu ◽  
Lin Xu ◽  
Pian-Pian Zhao ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Causal Effect ◽  
Genetic Risk Score ◽  
Final Analysis ◽  
Ultrasound Measurement ◽  
Mendelian Randomisation ◽  
Mineral Density ◽  
Medication Treatment ◽  
Weighted Genetic Risk Score ◽  
The Relationship

Objectives and methodsWith 432 513 samples from UK Biobank dataset, multivariable linear/logistic regression were used to estimate the relationship between psoriasis/psoriatic arthritis (PsA) and estimated bone mineral density (eBMD)/osteoporosis, controlling for potential confounders. Here, confounders were set in three ways: model0 (including age, height, weight, smoking and drinking), model1 (model0 +regular physical activity) and model2 (model1 +medication treatments). The eBMD was derived from heel ultrasound measurement. And 4904 patients with psoriasis and 847 patients with PsA were included in final analysis. Mendelian randomisation (MR) approach was used to evaluate the causal effect between them.ResultsLower eBMD were observed in patients with PsA than in controls in both model0 (β-coefficient=−0.014, p=0.0006) and model1 (β-coefficient=−0.013, p=0.002); however, the association disappeared when conditioning on treatment with methotrexate or ciclosporin (model2) (β-coefficient=−0.005, p=0.28), mediation analysis showed that 63% of the intermediary effect on eBMD was mediated by medication treatment (p<2E-16). Patients with psoriasis without arthritis showed no difference of eBMD compared with controls. Similarly, the significance of higher risk of osteopenia in patients with PsA (OR=1.27, p=0.002 in model0) could be eliminated by conditioning on medication treatment (p=0.244 in model2). Psoriasis without arthritis was not related to osteopenia and osteoporosis. The weighted Genetic Risk Score analysis found that genetically determined psoriasis/PsA were not associated with eBMD (p=0.24 and p=0.88). Finally, MR analysis showed that psoriasis/PsA had no causal effect on eBMD, osteoporosis and fracture.ConclusionsThe effect of PsA on osteoporosis was secondary (eg, medication) but not causal. Under this hypothesis, psoriasis without arthritis was not a risk factor for osteoporosis.

scholarly journals Lack of an association between gallstone disease and bilirubin levels with risk of colorectal cancer: a Mendelian randomisation analysis

2021 ◽  
Author(s):  
Richard Culliford ◽  
Alex J. Cornish ◽  
Philip J. Law ◽  
Susan M. Farrington ◽  
Kimmo Palin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Large Scale ◽  
Causal Effect ◽  
Gallstone Disease ◽  
Epidemiological Studies ◽  
Mendelian Randomisation ◽  
Linear Relationships ◽  
Potential Risk Factors ◽  
The Relationship ◽  
Circulating Levels

Abstract Background Epidemiological studies of the relationship between gallstone disease and circulating levels of bilirubin with risk of developing colorectal cancer (CRC) have been inconsistent. To address possible confounding and reverse causation, we examine the relationship between these potential risk factors and CRC using Mendelian randomisation (MR). Methods We used two-sample MR to examine the relationship between genetic liability to gallstone disease and circulating levels of bilirubin with CRC in 26,397 patients and 41,481 controls. We calculated the odds ratio per genetically predicted SD unit increase in log bilirubin levels (ORSD) for CRC and tested for a non-zero causal effect of gallstones on CRC. Sensitivity analysis was applied to identify violations of estimator assumptions. Results No association between either gallstone disease (P value = 0.60) or circulating levels of bilirubin (ORSD = 1.00, 95% confidence interval (CI) = 0.96–1.03, P value = 0.90) with CRC was shown. Conclusions Despite the large scale of this study, we found no evidence for a causal relationship between either circulating levels of bilirubin or gallstone disease with risk of developing CRC. While the magnitude of effect suggested by some observational studies can confidently be excluded, we cannot exclude the possibility of smaller effect sizes and non-linear relationships.

scholarly journals Osteoarthritis: Insights Offered by the Study of Bone Mass Genetics

2021 ◽  
Vol 19 (2) ◽  
pp. 115-122
Author(s):  
A. Hartley ◽  
C. L. Gregson ◽  
L. Paternoster ◽  
J. H. Tobias
Keyword(s):  
Bone Mass ◽  
Causal Effect ◽  
Mendelian Randomisation ◽  
Mineral Density ◽  
High Bone Mass ◽  
Increased Risk ◽  
High Bone ◽  
Genetic Mechanisms ◽  
Additional Support

Abstract Purpose of Review This paper reviews how bone genetics has contributed to our understanding of the pathogenesis of osteoarthritis. As well as identifying specific genetic mechanisms involved in osteoporosis which also contribute to osteoarthritis, we review whether bone mineral density (BMD) plays a causal role in OA development. Recent Findings We examined whether those genetically predisposed to elevated BMD are at increased risk of developing OA, using our high bone mass (HBM) cohort. HBM individuals were found to have a greater prevalence of OA compared with family controls and greater development of radiographic features of OA over 8 years, with predominantly osteophytic OA. Initial Mendelian randomisation analysis provided additional support for a causal effect of increased BMD on increased OA risk. In contrast, more recent investigation estimates this relationship to be bi-directional. However, both these findings could be explained instead by shared biological pathways. Summary Pathways which contribute to BMD appear to play an important role in OA development, likely reflecting shared common mechanisms as opposed to a causal effect of raised BMD on OA. Studies in HBM individuals suggest this reflects an important role of mechanisms involved in bone formation in OA development; however further work is required to establish whether the same applies to more common forms of OA within the general population.

scholarly journals Association of timing of menarche with depressive symptoms and depression in adolescence: Mendelian randomisation study

2017 ◽  
Vol 210 (1) ◽  
pp. 39-46 ◽  
Author(s):  
Maija-Eliina Sequeira ◽  
Sarah J. Lewis ◽  
Carolina Bonilla ◽  
George Davey Smith ◽  
Carol Joinson
Keyword(s):  
Depressive Symptoms ◽  
Risk Score ◽  
Causal Effect ◽  
Genetic Risk Score ◽  
Mendelian Randomisation ◽  
Age At Menarche ◽  
Genetic Score ◽  
Early Menarche ◽  
Timing Of Menarche ◽  
Effect Of Age

BackgroundObservational studies report associations between early menarche and higher levels of depressive symptoms and depression. However, no studies have investigated whether this association is causal.AimsTo determine whether earlier menarche is a causal risk factor for depressive symptoms and depression in adolescence.MethodThe associations between a genetic score for age at menarche and depressive symptoms at 14, 17 and 19 years, and depression at 18 years, were examined using Mendelian randomisation analysis techniques.ResultsUsing a genetic risk score to indicate earlier timing of menarche, we found that early menarche is associated with higher levels of depressive symptoms at 14 years (odds ratio per risk allele 1.02, 95% CI 1.005–1.04,n=2404). We did not find an association between the early menarche risk score and depressive symptoms or depression after age 14.ConclusionsOur results provide evidence for a causal effect of age at menarche on depressive symptoms at age 14.

scholarly journals Is Hyperuricemia, an Early-Onset Metabolic Disorder, Causally Associated with Cardiovascular Disease Events in Han Chinese?

2019 ◽  
Vol 8 (8) ◽  
pp. 1202 ◽  
Author(s):  
Kuang-Mao Chiang ◽  
Yuh-Chyuan Tsay ◽  
Ta-Chou Vincent Ng ◽  
Hsin-Chou Yang ◽  
Yen-Tsung Huang ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Metabolic Disorder ◽  
Disease Risk ◽  
Genetic Risk Score ◽  
Cardiovascular Disease Risk ◽  
Study Results ◽  
Weighted Genetic Risk Score ◽  
Low Hdl ◽  
The Relationship ◽  
Mr Study

Background: Serum uric acid (SUA) has gradually been recognized as a potential risk factor for cardiovascular disease (CVD). However, whether the relationship is causal remains controversial. Methods: We employed two methods to demonstrate the importance of SUA in CVD development. First, we examined the onset sequence of hyperuricemia in relation to five cardiometabolic (CM) diseases. Second, we conducted a Mendelian randomization (MR) study to causally infer the relationship between SUA and CVD. The information collected from the Cardiovascular Disease Risk Factors Two-Township Study (CVDFACTS) and Taiwan Biobank was used, respectively. Results: The onset sequence study showed that hyperuricemia and hypo-alpha-lipoproteinemia (low HDL-C) have earlier ages of onset than other CM diseases. For the MR analysis, the high weighted genetic risk score (WGRS) group had a significantly increased cumulative lifetime risk of CVD compared with the low WGRS group (OR = 1.62, (1.17−2.23), P = 0.003). Sensitivity analysis using the WGRS derived from other populations’ SUA-influential SNPs revealed similar results. Conclusions: We showed that hyperuricemia is an earlier-onset metabolic disorder than hypertension, hypertriglyceridemia, and diabetes mellitus, indicating that high SUA plays an upstream role in CM development. Moreover, our MR study results support the idea that hyperuricemia may play a causal role in CVD development. Further validation studies in more populations are needed.

scholarly journals Investigation of glycaemic traits in psychiatric disorders using Mendelian randomisation revealed a causal relationship with anorexia nervosa

2020 ◽  
Author(s):  
Danielle M. Adams ◽  
William R. Reay ◽  
Michael P. Geaghan ◽  
Murray J. Cairns
Keyword(s):  
Anorexia Nervosa ◽  
Psychiatric Disorders ◽  
Observational Studies ◽  
Causal Effect ◽  
Mendelian Randomisation ◽  
Fasting Insulin ◽  
Multiple Testing Correction ◽  
Insulin Levels ◽  
Glycaemic Traits ◽  
The Relationship

Abstract Data from observational studies have suggested an involvement of abnormal glycaemic regulation in the pathophysiology of psychiatric illness. This may be an attractive target for clinical intervention as glycaemia can be modulated by both lifestyle factors and pharmacological agents. However, observational studies are inherently confounded, and therefore, causal relationships cannot be reliably established. We employed genetic variants rigorously associated with three glycaemic traits (fasting glucose, fasting insulin, and glycated haemoglobin) as instrumental variables in a two-sample Mendelian randomisation analysis to investigate the causal effect of these measures on the risk for eight psychiatric disorders. A significant protective effect of a natural log transformed pmol/L increase in fasting insulin levels was observed for anorexia nervosa after the application of multiple testing correction (OR = 0.48 [95% CI: 0.33-0.71]—inverse-variance weighted estimate). There was no consistently strong evidence for a causal effect of glycaemic factors on the other seven psychiatric disorders considered. The relationship between fasting insulin and anorexia nervosa was supported by a suite of sensitivity analyses, with no statistical evidence of instrument heterogeneity or horizontal pleiotropy. Further investigation is required to explore the relationship between insulin levels and anorexia.

scholarly journals Is a large eye size a risk factor for myopia? A Mendelian randomization study

2017 ◽  
Author(s):  
Keyword(s):  
Risk Factor ◽  
Risk Score ◽  
Refractive Error ◽  
Axial Length ◽  
Genetic Risk ◽  
Causal Effect ◽  
Genetic Risk Score ◽  
Mendelian Randomisation ◽  
Corneal Curvature ◽  
Eye Size

AbstractMyopia (nearsightedness) is an increasingly common cause of irreversible visual impairment. The ocular structures with greatest impact on refractive error are corneal curvature and axial length. Emmetropic eyes range in size within and across species, yet possess a balance between corneal curvature and axial length that is under genetic control. This scaling goes awry in myopia: 1 mm axial elongation is associated with ~3 Dioptres (D) myopia. Evidence that eye size prior to onset is a risk factor for myopia is conflicting. We applied Mendelian randomisation to test for a causal effect of eye size on refractive error. Genetic variants associated with corneal curvature identified in emmetropic eyes (22,180 individuals) were used as instrumental variables and tested for association with refractive error (139,697 individuals). A genetic risk score for the variants was tested for association with corneal curvature and axial length in an independent sample (315 emmetropes). The genetic risk score explained 2.3% (P=0.007) and 2.7% (P=0.002) of the variance in corneal curvature and axial length, respectively, in the independent sample, confirming these variants are predictive of eye size in emmetropes. The estimated causal effect of eye size on refractive error was + 1.41 D (95% CI. 0.65 to 2.16) less myopic refractive error per mm flatter cornea (P<0.001), corresponding to +0.48 D (95% CI. 0.22 to 0.73) more hypermetropic refractive error for an eye with a 1mm longer axial length. These results do not support the hypothesis that a larger eye size is a risk factor for myopia. We conclude the genetic determinants of normal eye size are not shared with those influencing susceptibility to myopia.

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