Association between biological ageing and periodontitis: Evidence from a cross-sectional survey and multi-omics Mendelian randomization analysis. Journal of clinical periodontology AIM:To investigate the relationship and potential causality between biological ageing and periodontitis. MATERIALS AND METHODS:We obtained the National Health and Nutrition Examination Survey (NHANES) and genome-wide association study (GWAS) summary statistics as well as single-cell sequencing data. Multivariate regression analysis based on cross-sectional data, Mendelian randomization (MR) and multi-omics integration analysis were employed to explore the causal association and potential molecular mechanisms between biological ageing and periodontitis. Additionally, two-step MR mediation analysis explored the risk factors in biological ageing-mediated periodontitis. RESULTS:We analysed data from 3189 participants in the NHANES data and found that higher biological age was associated with increased risk of periodontitis. MR analyses revealed causal associations between biological age measures and periodontitis risk. Frailty (odds ratio [OR] = 2.08, 95% confidence interval [CI]: 1.04-4.18, p = .039) and GrimAge acceleration (OR = 1.16, 95% CI: 1.01-1.32, p = .033) were causally associated with periodontitis risk, and these results were validated in a large-scale meta-periodontitis GWAS dataset. Additionally, the risk effects of body mass index, waist circumference and lifetime smoking on periodontitis were partially mediated by frailty and GrimAge acceleration. CONCLUSIONS:Evidence from cross-sectional survey and MR analysis suggests that biological ageing increases the risk of periodontitis. Additionally, improving the associated risk factors can help prevent both ageing and periodontitis. 10.1111/jcpe.14040

The risk of Alzheimer's disease and cognitive impairment characteristics in eight mental disorders: A UK Biobank observational study and Mendelian randomization analysis. Alzheimer's & dementia : the journal of the Alzheimer's Association INTRODUCTION:The cognitive impairment patterns and the association with Alzheimer's disease (AD) in mental disorders remain poorly understood. METHODS:We analyzed data from 486,297 UK Biobank participants, categorizing them by mental disorder history to identify the risk of AD and the cognitive impairment characteristics. Causation was further assessed using Mendelian randomization (MR). RESULTS:AD risk was higher in individuals with bipolar disorder (BD; hazard ratio [HR] = 2.37, P < 0.01) and major depressive disorder (MDD; HR = 1.63, P < 0.001). MR confirmed a causal link between BD and AD (OR= 1.098), as well as obsessive-compulsive disorder (OCD) and AD (OR= 1.050). Cognitive impairments varied, with BD and schizophrenia showing widespread deficits, and OCD affecting complex task performance. DISCUSSION:Observational study and MR provide consistent evidence that mental disorders are independent risk factors for AD. Mental disorders exhibit distinct cognitive impairment prior to dementia, indicating the potential different mechanisms in AD pathogenesis. Early detection of these impairments in mental disorders is crucial for AD prevention. HIGHLIGHTS:This is the most comprehensive study that investigates the risk and causal relationships between a history of mental disorders and the development of Alzheimer's disease (AD), alongside exploring the cognitive impairment characteristics associated with different mental disorders. Individuals with bipolar disorder (BD) exhibited the highest risk of developing AD (hazard ratio [HR] = 2.37, P < 0.01), followed by those with major depressive disorder (MDD; HR = 1.63, P < 0.001). Individuals with schizophrenia (SCZ) showed a borderline higher risk of AD (HR = 2.36, P = 0.056). Two-sample Mendelian randomization (MR) confirmed a causal association between BD and AD (OR= 1.098, P < 0.05), as well as AD family history (proxy-AD, OR= 1.098, P < 0.001), and kept significant after false discovery rate correction. MR also identified a nominal significant causal relationship between the obsessive-compulsive disorder (OCD) spectrum and AD (OR= 1.050, P < 0.05). Individuals with SCZ, BD, and MDD exhibited impairments in multiple cognitive domains with distinct patterns, whereas those with OCD showed only slight declines in complex tasks. 10.1002/alz.14049

Identifying the association between depression and constipation: An observational study and Mendelian randomization analysis. Journal of affective disorders BACKGROUND:Both depression and constipation are universal disorders that seriously affect quality of life. But the phenotypic relationship and causality between depression and constipation are still unclear. METHODS:We first assessed phenotypic relationships by logistic regression analysis using large-scale data extracted from the National Health and Nutrition Examination Survey (N = 11,585). We then evaluated causality by bidirectional two-sample mendelian randomization (MR) analysis using Genome-wide association study (GWAS) data (depression: N = 807,553; constipation: N = 377,277). To investigate whether depression severity affects the causal relationship between depression and constipation, we conducted a further MR study on GWAS data of major depression (N = 480,359). RESULTS:About 11.31 % of the participants in the constipation group suffered from depression, which was significantly higher than the normal bowel group (6.09 %). The observational study showed a positive correlation between depression and constipation (OR = 1.968, 95%CI = 1.530-2.532). Besides, the risk of constipation was higher in participants with severe depression (OR = 2.294, 95%CI = 1.538-3.422) than in participants with mild depression (OR = 1.549, 95%CI = 1.242-1.932). Bidirectional MR analysis revealed an obviously causal effect of depression on constipation, but no causal effect of constipation on depression. In addition, the MR analysis also revealed a causal relationship between major depression and constipation. LIMITATION:The exact mechanism by which depression affects constipation is still unclear. CONCLUSION:This study reveals a positive correlation between depression and constipation and the causal effect of depression on constipation. Clinicians should keep the risk of constipation in mind when treating patients with depression. 10.1016/j.jad.2024.05.124

Investigating the relationship between depression and breast cancer: observational and genetic analyses. BMC medicine BACKGROUND:Both depression and breast cancer (BC) contribute to a substantial global burden of morbidity and mortality among women, and previous studies have observed a potential depression-BC link. We aimed to comprehensively characterize the phenotypic and genetic relationships between depression and BC. METHODS:We first evaluated phenotypic association using longitudinal follow-up data from the UK Biobank (N = 250,294). We then investigated genetic relationships leveraging summary statistics from the hitherto largest genome-wide association study of European individuals conducted for depression (N = 500,199), BC (N = 247,173), and its subtypes based on the status of estrogen receptor (ER + : N = 175,475; ER - : N = 127,442). RESULTS:Observational analysis suggested an increased hazard of BC in depression patients (HR = 1.10, 95%CIs = 0.95-1.26). A positive genetic correlation between depression and overall BC was observed ([Formula: see text] = 0.08, P = 3.00 × 10), consistent across ER + ([Formula: see text] = 0.06, P = 6.30 × 10) and ER - subtypes ([Formula: see text] = 0.08, P = 7.20 × 10). Several specific genomic regions showed evidence of local genetic correlation, including one locus at 9q31.2, and four loci at, or close, to 6p22.1. Cross-trait meta-analysis identified 17 pleiotropic loci shared between depression and BC. TWAS analysis revealed five shared genes. Bi-directional Mendelian randomization suggested risk of depression was causally associated with risk of overall BC (OR = 1.12, 95%Cis = 1.04-1.19), but risk of BC was not causally associated with risk of depression. CONCLUSIONS:Our work demonstrates a shared genetic basis, pleiotropic loci, and a putative causal relationship between depression and BC, highlighting a biological link underlying the observed phenotypic relationship; these findings may provide important implications for future studies aimed reducing BC risk. 10.1186/s12916-023-02876-w