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Association of Cortisol Levels With Neuropsychiatric Functions: A Mendelian Randomization Analysis.

ABSTRACT: Aim: The conflicting evidence as to whether a real association exists between cortisol levels and depression lends support to adopting a Mendelian randomization approach to investigate whether cortisol levels have a causal effect with depression. Methods: Single nucleotide polymorphisms (SNPs) associated with serum morning plasma cortisol level and salivary cortisol level from CORNET consortium (12,597 participants) were proposed as instrumental variables. The primary outcome was depression, and the secondary outcomes were neuroticism and cognitive performance. Summary-level statistics were extracted from the Social Science Genetic Association Consortium including the United Kingdom Biobank cohort (105,739 subjects). Multiple analysis methods (inverse-variance weighted method, max likelihood method, weighted median estimator, model-based estimation, heterogeneity-penalized method, and MR-Egger regression) were applied to test the stability of the summary causal estimate. Results: Weighted median analysis estimated that the effect of serum morning cortisol on depression score was 0.027 per standard deviation increase of cortisol (95% CI, 0.000-0.054; p = 0.043). Other sensitivity analysis suggested similar results suggesting the result was robust. No evidence of pleiotropy (MR-Egger intercept, -0.002; p = 0.739) was observed. The effect of serum cortisol on neuroticism was 0.030 (95% CI, 0.008-0.052; p = 0.006) by weighted median estimator. None of the methods observed the effect of serum cortisol level on cognitive function. As for the effect of salivary cortisol level, no method obtained a p-value lower than 0.05 in any of the outcomes. Conclusion: Mendelian randomization analysis provided evidence that a genetic predisposition to higher serum morning cortisol level was associated with increased depression score.

SUBMITTER: Zhou X

PROVIDER: S-EPMC6706785 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Association of Cortisol Levels With Neuropsychiatric Functions: A Mendelian Randomization Analysis.

Zhou Xiang X Qiao Nidan N

Frontiers in endocrinology 20190816

<b>Aim:</b> The conflicting evidence as to whether a real association exists between cortisol levels and depression lends support to adopting a Mendelian randomization approach to investigate whether cortisol levels have a causal effect with depression. <b>Methods:</b> Single nucleotide polymorphisms (SNPs) associated with serum morning plasma cortisol level and salivary cortisol level from CORNET consortium (12,597 participants) were proposed as instrumental variables. The primary outcome was d ...[more]

PMID: 31474942

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Project description:BackgroundCross-sectional studies have shown that objectively measured physical activity is associated with childhood adiposity, and a strong inverse dose-response association with body mass index (BMI) has been found. However, few studies have explored the extent to which this association reflects reverse causation. We aimed to determine whether childhood adiposity causally influences levels of physical activity using genetic variants reliably associated with adiposity to estimate causal effects.Methods and findingsThe Avon Longitudinal Study of Parents and Children collected data on objectively assessed activity levels of 4,296 children at age 11 y with recorded BMI and genotypic data. We used 32 established genetic correlates of BMI combined in a weighted allelic score as an instrumental variable for adiposity to estimate the causal effect of adiposity on activity. In observational analysis, a 3.3 kg/m² (one standard deviation) higher BMI was associated with 22.3 (95% CI, 17.0, 27.6) movement counts/min less total physical activity (p = 1.6×10⁻¹⁶), 2.6 (2.1, 3.1) min/d less moderate-to-vigorous-intensity activity (p = 3.7×10⁻²⁹), and 3.5 (1.5, 5.5) min/d more sedentary time (p = 5.0×10⁻⁴). In Mendelian randomization analyses, the same difference in BMI was associated with 32.4 (0.9, 63.9) movement counts/min less total physical activity (p = 0.04) (∼5.3% of the mean counts/minute), 2.8 (0.1, 5.5) min/d less moderate-to-vigorous-intensity activity (p = 0.04), and 13.2 (1.3, 25.2) min/d more sedentary time (p = 0.03). There was no strong evidence for a difference between variable estimates from observational estimates. Similar results were obtained using fat mass index. Low power and poor instrumentation of activity limited causal analysis of the influence of physical activity on BMI.ConclusionsOur results suggest that increased adiposity causes a reduction in physical activity in children and support research into the targeting of BMI in efforts to increase childhood activity levels. Importantly, this does not exclude lower physical activity also leading to increased adiposity, i.e., bidirectional causation.

Dataset Information

Association of Cortisol Levels With Neuropsychiatric Functions: A Mendelian Randomization Analysis.

Publications

Association of Cortisol Levels With Neuropsychiatric Functions: A Mendelian Randomization Analysis.

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