Dataset Information

Association of sleep traits with risk of hypertensive disorders of pregnancy: a mendelian randomization study.

ABSTRACT:

Background

Unhealthy sleep patterns are common during pregnancy and have been associated with an increased risk of developing hypertensive disorders of pregnancy (HDPs) in observational studies. However, the causality underlying these associations remains uncertain. This study aimed to evaluate the potential causal association between seven sleep traits and the risk of HDPs using a two-sample Mendelian randomization study.

Methods

Genome-wide association study (GWAS) summary statistics were obtained from the FinnGen consortium, UK Biobank, and other prominent consortia, with a focus on individuals of European ancestry. The primary analysis utilized an inverse-variance-weighted MR approach supplemented by sensitivity analyses to mitigate potential biases introduced by pleiotropy. Furthermore, a two-step MR framework was employed for mediation analyses.

Results

The data analyzed included 200 000-500 000 individuals for each sleep trait, along with approximately 15 000 cases of HDPs. Genetically predicted excessive daytime sleepiness (EDS) exhibited a significant association with an increased risk of HDPs [odds ratio (OR) 2.96, 95% confidence interval (95% CI) 1.40-6.26], and the specific subtype of preeclampsia/eclampsia (OR 2.97, 95% CI 1.06-8.3). Similarly, genetically predicted obstructive sleep apnea (OSA) was associated with a higher risk of HDPs (OR 1.27, 95% CI 1.09-1.47). Sensitivity analysis validated the robustness of these associations. Mediation analysis showed that BMI mediated approximately 25% of the association between EDS and HDPs, while mediating up to approximately 60% of the association between OSA and the outcomes. No statistically significant associations were observed between other genetically predicted sleep traits, such as chronotype, daytime napping, sleep duration, insomnia, snoring, and the risk of HDPs.

Conclusion

Our findings suggest a causal association between two sleep disorders, EDS and OSA, and the risk of HDPs, with BMI acting as a crucial mediator. EDS and OSA demonstrate promise as potentially preventable risk factors for HDPs, and targeting BMI may represent an alternative treatment strategy to mitigate the adverse impact of sleep disorders.

SUBMITTER: Zhao H

PROVIDER: S-EPMC11296273 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature

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Publications

Association of sleep traits with risk of hypertensive disorders of pregnancy: a mendelian randomization study.

Zhao Huanqiang H Wen Ping P Xiong Yu Y Xu Qixin Q Zi Yang Y Zheng Xiujie X Chen Shiguo S Qin Yueyuan Y Shao Shuyi S Tu Xinzhi X Zheng Zheng Z Li Xiaotian X

Journal of hypertension 20240523 9

<h4>Background</h4>Unhealthy sleep patterns are common during pregnancy and have been associated with an increased risk of developing hypertensive disorders of pregnancy (HDPs) in observational studies. However, the causality underlying these associations remains uncertain. This study aimed to evaluate the potential causal association between seven sleep traits and the risk of HDPs using a two-sample Mendelian randomization study.<h4>Methods</h4>Genome-wide association study (GWAS) summary stati ...[more]

PMID: 38780189

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Project description:BackgroundHypertensive disorders of pregnancy (HDP) are associated with an increased risk of stroke later in life in multiparous women. However, causality of these associations remains unclear. This study employed 2-sample univariate and multivariate Mendelian randomization (MR) to assess the causal connection between HDP and stroke.MethodsGenetic variants for HDP and two subtypes were identified from recent large-scale genome-wide association studies and the FinnGen consortium. Stroke summary data were obtained from the MEGASTROKE consortium. The primary analytical approach for univariate MR was the inverse variance weighting method. Sensitivity analyses incorporated methods such as MR-Egger regression, weighted median, and maximum likelihood to ascertain the robustness of the results. Additionally, multivariable MR analyses were conducted to account for potential associative effects of hypertension and type 2 diabetes.ResultsGenetically predicted HDP was associated with a high risk of large artery atherosclerosis (odds ratio [OR]=1.50, 95% confidence interval [CI]: 1.17-1.91, P=1.13×10-3) and small vessel stroke (OR=1.29, 95% CI: 1.20-1.50, P=1.52×10-3). HDP may also correlate with ischemic stroke (OR=1.13, 95% CI: 1.04-1.23, P=4.99×10-3) and stroke (OR=1.11, 95% CI: 1.03-1.20, P=8.85×10-3). An elevated risk of small vessel stroke (OR=1.20, 95% CI: 1.01-1.43, P=3.74×10-2) and large artery atherosclerosis (OR=1.22, 95% CI: 1.01-1.47, P=4.07×10-2) may be related with genetically predicted susceptibility to gestational hypertension. Genetically predicted susceptibility to preeclampsia or eclampsia may be associated with an increased risk of stroke (OR = 1.10, 95% CI: 1.02-1.19, P = 1.16×10-2) and ischemic stroke (OR = 1.10, 95% CI: 1.02-1.20, P = 1.84×10-2). Type 2 diabetes mellitus and hypertension were identified as significant factors contributing to the association between HDP and stroke.ConclusionsThis study provides genetic evidence supporting an association between HDP and increased stroke risk bolstering HDP as a cerebrovascular risk factor.

Project description:Currently, the causal association between sleep disorders and rheumatoid arthritis (RA) has been poorly understood. In this two-sample Mendelian randomization (TSMR) study, we tried to explore whether sleep disorders are causally associated with RA. Seven sleep-related traits were chosen from the published Genome-Wide Association Study (GWAS): short sleep duration, frequent insomnia, any insomnia, sleep duration, getting up, morningness (early-to-bed/up habit), and snoring, 27, 53, 57, 57, 70, 274, and 42 individual single-nucleotide polymorphisms (SNPs) (P < 5 × 10-8) were obtained as instrumental variables (IVs) for these sleep-related traits. Outcome variables were obtained from a public GWAS study that included 14,361 cases and 43,923 European Ancestry controls. The causal relationship between sleep disturbances and RA risk were evaluated by a two-sample Mendelian randomization (MR) analysis using inverse variance weighted (IVW), MR-Egger regression, weighted median, and weight mode methods. MR-Egger Regression and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) were used to test for horizontal pleomorphism and outliers. There was no evidence of a link between RA and frequent insomnia (IVW, odds ratio (OR): 0.99; 95% interval (CI): 0.84-1.16; P = 0.858), any insomnia (IVW, OR: 1.09; 95% CI: 0.85-1.42; P = 0.489), sleep duration (IVW, OR: 0.65, 95% CI: 0.38-1.10, P = 0.269), getting up (IVW, OR: 0.56, 95% CI: 0.13-2.46, P = 0.442), morningness (IVW, OR: 2.59; 95% CI: 0.73-9.16; P = 0.142), or snoring (IVW, OR: 0.95; 95% CI: 0.68-1.33; P = 0.757). Short sleep duration (6h) had a causal effect on RA, as supported by IVW and weighted median (OR: 1.47, 95% CI: 1.12-1.94, P = 0.006; OR: 1.43, 95%CI:1.01-2.05, P = 0.047). Sensitivity analysis showed that the results were stable. Our findings imply that short sleep duration is causally linked to an increased risk of RA. Therefore, sleep length should be considered in disease models, and physicians should advise people to avoid short sleep duration practices to lower the risk of RA.

Project description:ObjectiveTo use mendelian randomisation to investigate whether 25-hydroxyvitamin D concentration has a causal effect on gestational hypertension or pre-eclampsia.DesignOne and two sample mendelian randomisation analyses.SettingTwo European pregnancy cohorts (Avon Longitudinal Study of Parents and Children, and Generation R Study), and two case-control studies (subgroup nested within the Norwegian Mother and Child Cohort Study, and the UK Genetics of Pre-eclampsia Study).Participants7389 women in a one sample mendelian randomisation analysis (751 with gestational hypertension and 135 with pre-eclampsia), and 3388 pre-eclampsia cases and 6059 controls in a two sample mendelian randomisation analysis.ExposuresSingle nucleotide polymorphisms in genes associated with vitamin D synthesis (rs10741657 and rs12785878) and metabolism (rs6013897 and rs2282679) were used as instrumental variables.Main outcome measuresGestational hypertension and pre-eclampsia defined according to the International Society for the Study of Hypertension in Pregnancy.ResultsIn the conventional multivariable analysis, the relative risk for pre-eclampsia was 1.03 (95% confidence interval 1.00 to 1.07) per 10% decrease in 25-hydroxyvitamin D level, and 2.04 (1.02 to 4.07) for 25-hydroxyvitamin D levels <25 nmol/L compared with ≥75 nmol/L. No association was found for gestational hypertension. The one sample mendelian randomisation analysis using the total genetic risk score as an instrument did not provide strong evidence of a linear effect of 25-hydroxyvitamin D on the risk of gestational hypertension or pre-eclampsia: odds ratio 0.90 (95% confidence interval 0.78 to 1.03) and 1.19 (0.92 to 1.52) per 10% decrease, respectively. The two sample mendelian randomisation estimate gave an odds ratio for pre-eclampsia of 0.98 (0.89 to 1.07) per 10% decrease in 25-hydroxyvitamin D level, an odds ratio of 0.96 (0.80 to 1.15) per unit increase in the log(odds) of 25-hydroxyvitamin D level <75 nmol/L, and an odds ratio of 0.93 (0.73 to 1.19) per unit increase in the log(odds) of 25-hydroxyvitamin D levels <50 nmol/L.ConclusionsNo strong evidence was found to support a causal effect of vitamin D status on gestational hypertension or pre-eclampsia. Future mendelian randomisation studies with a larger number of women with pre-eclampsia or more genetic instruments that would increase the proportion of 25-hydroxyvitamin D levels explained by the instrument are needed.

Dataset Information

Association of sleep traits with risk of hypertensive disorders of pregnancy: a mendelian randomization study.

Background

Methods

Results

Conclusion

Publications

Association of sleep traits with risk of hypertensive disorders of pregnancy: a mendelian randomization study.

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