Dataset Information

Associations of statin use with motor performance and myalgia may be modified by 25-hydroxyvitamin D: findings from a British birth cohort.

ABSTRACT: The objective was to examine whether: (1) statin use was associated with muscle related outcomes at age 60-64, (2) these associations were modified by 25-hydroxyvitamin D (25(OH)D) status and explained by inflammation, body-size or lifestyle in a British birth cohort. Markers of myalgia (intrusive body pain) and myopathy (self-reported and performance-based measures) were examined in 734 men and 822 women (MRC National Survey of Health and Development). Statin use was associated with intrusive body pain, difficulty climbing stairs and slower chair rise speed. Some associations were modified by 25(OH)D e.g. the association with intrusive body pain was evident in the insufficient (13-20?ng/l) and deficient (<13?ng/l) 25(OH)D status groups (OR?=?2.6,95% CI 1.7-1.1; OR?=?1.8,95% CI 1.2-2.8, respectively) but not in those with status >20?ng/l (OR?=?0.8,95% CI 0.5-1.4) (p?=?0.003 for interaction). Associations were maintained in fully adjusted models of intrusive body pain and difficulty climbing stairs, but for chair rise speed they were fully accounted for by inflammation, body-size and lifestyle. In a nationally representative British population in early old age, statin use was associated with lower limb muscle-related outcomes, and some were only apparent in those with 25(OH)D status below 20?ng/l. Given 25(OH)D is modifiable in clinical practice, future studies should consider the links between 25(OH)D status and muscle related outcomes.

SUBMITTER: Sharma N

PROVIDER: S-EPMC5529559 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Associations of statin use with motor performance and myalgia may be modified by 25-hydroxyvitamin D: findings from a British birth cohort.

Sharma Nikhil N Cooper Rachel R Kuh Diana D Shah Imran I

Scientific reports 20170726 1

The objective was to examine whether: (1) statin use was associated with muscle related outcomes at age 60-64, (2) these associations were modified by 25-hydroxyvitamin D (25(OH)D) status and explained by inflammation, body-size or lifestyle in a British birth cohort. Markers of myalgia (intrusive body pain) and myopathy (self-reported and performance-based measures) were examined in 734 men and 822 women (MRC National Survey of Health and Development). Statin use was associated with intrusive b ...[more]

PMID: 28747665

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Project description:BackgroundPrevious observational studies have revealed the association between serum uric acid and 25-hydroxyvitamin D. However, the causality and the direction of the associations remain unknown. Thus, we performed a two-sample bidirectional Mendelian Randomization (MR) analysis to investigate the causal association between uric acid and 25-hydroxyvitamin D and to determine the direction of the association.MethodBased on the summary-level GWAS data from large genome-wide association studies, several steps were taken in our analysis to select eligible single-nucleotide polymorphisms (SNPs), which were strongly related to exposure as the instrumental variables. We used different analytical methods, such as inverse-variance weighting (IVW) method, weighted median, MR-Egger regression, and weighted mode method, to make our result more robust and reliable. The IVW method was used as the primary analysis. The Cochran's Q test, MR-Egger intercept test, MR-PRESSO method, and "leave-one-out" sensitivity analysis was performed to evaluate the heterogeneities, horizontal pleiotropy, and robustness of the results. MR analyses were also conducted using genetic risk scores (GRS) as instrumental variables in both directions by using the same summary-level GWAS data.ResultsOur two-sample MR analysis suggested a causal association of genetically predicted uric acid on 25-hydroxyvitamin D [IVW method: β(SE), -0.0352(0.0149); p = 0.0178], which suggested that a per mg/dl increase in uric acid was associated with a decrease of 0.74 nmol/L of 25-hydroxyvitamin D, and the above results remained stable in the sensitivity analysis. By contrast, four MR methods suggested no causal relationship of 25-hydroxyvitamin D on serum uric acid [IVW β(SE), 0.0139 (0.0635); p = 0.826; MR-Egger β(SE), 0.0671 (0.108); p = 0.537; weighted median β(SE), 0.0933 (0.0495); p = 0.0598; weighted mode β(SE), 0.0562 (0.0463); p = 0.228, respectively]. After excluding the SNPs, which were associated with confounding factors and outlier SNPs, the IVW method suggested that there was still no causal association of 25-hydroxyvitamin D on serum uric acid. The GRS approach showed similar results.ConclusionsSerum uric acid may causally affect the 25-hydroxyvitamin D levels, whereas the causal role of 25-hydroxyvitamin D on uric acid was not supported in our MR analysis. Our findings suggest that increased levels of uric acid should prompt investigation for vitamin D deficiency.

Project description:BackgroundPrevious research indicated that birth order was associated with physical health outcomes in adulthood. However, evidence on its association with mental health was lacking. The aim of this study was to investigate if birth order was associated with mental wellbeing and psychological distress at mid-life, stratified by gender, and taking into account confounding factors in childhood and adulthood.MethodThe sample consisted of 9,354 participants of the 1970 British Cohort Study (BCS70). The Warwick Edinburgh Mental Wellbeing Scale (WEMWBS), the Malaise Index and attending a doctor's consultation in the past year for a mental health issue at age forty-two were used to assess mental wellbeing and psychological distress in midlife. Birth order was ascertained via a parental questionnaire and referred to the numerical birth position of the participants. The associations between birth order, mental wellbeing and psychological distress were tested using linear and logistic regression adjusting for birth characteristics: smoking during pregnancy, maternal age, mother's marital status, father's employment, region of birth, parental years of education and parental social class, and factors at age 42: years of education, employment status and partnership status. Potential mediating variables including breastfeeding and birthweight at birth and parental separation and conduct disorder measured at age ten were also taken into account.ResultsWe find no evidence to support an association between birth order and midlife psychological distress or attending a doctor's consultation in both men and women. In unadjusted analysis, there was an association between birth order four and above and a reduced WEMWBS score of -0.79 (95% CI -1.57, -0.02) in men only. This association was attenuated after adjusting for birth characteristics and mediators at birth (0.86, 95% -1.78, 0.07) but was maintained once conduct disorder at age 10 was accounted for (-1.19, 95% CI -2.28, -0.09). However, this association was attenuated once again after adjusting for employment status, years in education and partnership status in adulthood (-1.04, 95% CI -2.11, 0.03).ConclusionsIn this study, birth order was not associated with psychological distress or having a mental health issue at midlife. Accounting for employment status, years of education and partnership status in adulthood attenuated the relationship between birth order and mental wellbeing.

Project description:CONTEXT:Lower serum 25-hydroxyvitamin D concentrations are associated with greater risks of many chronic diseases across large, prospective community-based studies. Substrate 25-hydroxyvitamin D must be converted to 1,25-dihydroxyvitamin D for full biological activity, and complex metabolic pathways suggest that interindividual variability in vitamin D metabolism may alter the clinical consequences of measured serum 25-hydroxyvitamin D. OBJECTIVE:To investigate whether common variation within genes encoding the vitamin D-binding protein, megalin, cubilin, CYP27B1, CYP24A1, and the vitamin D receptor (VDR) modify associations of low 25-hydroxyvitamin D with major clinical outcomes. DESIGN, SETTING, AND PARTICIPANTS:Examination of 141 single-nucleotide polymorphisms in a discovery cohort of 1514 white participants (who were recruited from 4 US regions) from the community-based Cardiovascular Health Study. Participants had serum 25-hydroxyvitamin D measurements in 1992-1993 and were followed up for a median of 11 years (through 2006). Replication meta-analyses were conducted across the independent, community-based US Health, Aging, and Body Composition (n = 922; follow-up: 1998-1999 through 2005), Italian Invecchiare in Chianti (n = 835; follow-up: 1998-2000 through 2006), and Swedish Uppsala Longitudinal Study of Adult Men (n = 970; follow-up: 1991-1995 through 2008) cohort studies. MAIN OUTCOME MEASURE:Composite outcome of incident hip facture, myocardial infarction, cancer, and mortality over long-term follow-up. RESULTS:Interactions between 5 single-nucleotide polymorphisms and low 25-hydroxyvitamin D concentration were identified in the discovery phase and 1 involving a variant in the VDR gene replicated in independent meta-analysis. Among Cardiovascular Health Study participants, low 25-hydroxyvitamin D concentration was associated with hazard ratios for risk of the composite outcome of 1.40 (95% CI, 1.12-1.74) for those who had 1 minor allele at rs7968585 and 1.82 (95% CI, 1.31-2.54) for those with 2 minor alleles at rs7968585. In contrast, there was no evidence of an association (estimated hazard ratio, 0.93 [95% CI, 0.70-1.24]) among participants who had 0 minor alleles at this single-nucleotide polymorphism. CONCLUSION:Known associations of low 25-hydroxyvitamin D with major health outcomes may vary according to common genetic differences in the vitamin D receptor.

Dataset Information

Associations of statin use with motor performance and myalgia may be modified by 25-hydroxyvitamin D: findings from a British birth cohort.

Publications

Associations of statin use with motor performance and myalgia may be modified by 25-hydroxyvitamin D: findings from a British birth cohort.

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