Phenomics (Cham, Switzerland)最新文献

{"title":"A Genome-Wide Association Study for Susceptibility to Axial Length in Highly Myopic Eyes.","authors":"Qiang Lu, Yu Du, Ye Zhang, Yuxi Chen, Hao Li, Wenwen He, Yating Tang, Zhennan Zhao, Yinglei Zhang, Jihong Wu, Xiangjia Zhu, Yi Lu","doi":"10.1007/s43657-022-00082-x","DOIUrl":"10.1007/s43657-022-00082-x","url":null,"abstract":"<p><p>High myopia has long been highly prevalent worldwide with a largely yet unexplained genetic contribution. To identify novel susceptibility genes for axial length (AL) in highly myopic eyes, a genome-wide association study (GWAS) was performed using the genomic dataset of 350 deep whole-genome sequencing data from highly myopic patients. Top single nucleotide polymorphisms (SNPs) were functionally annotated. Immunofluorescence staining, quantitative polymerase chain reaction, and western blot were performed using neural retina of form-deprived myopic mice. Enrichment analyses were further performed. We identified the four top SNPs and found that <i>ADAM Metallopeptidase With Thrombospondin Type 1 Motif 16</i> (<i>ADAMTS16</i>) and <i>Phosphatidylinositol Glycan Anchor Biosynthesis Class Z</i> (<i>PIGZ</i>) had the potential of clinical significance. Animal experiments confirmed that PIGZ expression could be observed and showed higher expression level in form-deprived mice, especially in the ganglion cell layer. The messenger RNA (mRNA) levels of both <i>ADAMTS16</i> and <i>PIGZ</i> were significantly higher in the neural retina of form-deprived eyes (<i>p</i> = 0.005 and 0.007 respectively), and both proteins showed significantly upregulated expression in the neural retina of deprived eyes (<i>p</i> = 0.004 and 0.042, respectively). Enrichment analysis revealed a significant role of cellular adhesion and signal transduction in AL, and also several AL-related pathways including circadian entrainment and inflammatory mediator regulation of transient receptor potential channels were proposed. In conclusion, the current study identified four novel SNPs associated with AL in highly myopic eyes and confirmed that the expression of ADAMTS16 and PIGZ was significantly upregulated in neural retina of deprived eyes. Enrichment analyses provided novel insight into the etiology of high myopia and opened avenues for future research interest.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43657-022-00082-x.</p>","PeriodicalId":74435,"journal":{"name":"Phenomics (Cham, Switzerland)","volume":"3 3","pages":"255-267"},"PeriodicalIF":0.0,"publicationDate":"2022-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10260730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9661059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Measurement of Cerebral Oxygen Extraction Fraction Using Quantitative BOLD Approach: A Review.","authors":"Hongwei Li, Chengyan Wang, Xuchen Yu, Yu Luo, He Wang","doi":"10.1007/s43657-022-00081-y","DOIUrl":"10.1007/s43657-022-00081-y","url":null,"abstract":"<p><p>Quantification of brain oxygenation and metabolism, both of which are indicators of the level of brain activity, plays a vital role in understanding the cerebral perfusion and the pathophysiology of brain disorders. Magnetic resonance imaging (MRI), a widely used clinical imaging technique, which is very sensitive to magnetic susceptibility, has the possibility of substituting positron emission tomography (PET) in measuring oxygen metabolism. This review mainly focuses on the quantitative blood oxygenation level-dependent (qBOLD) method for the evaluation of oxygen extraction fraction (OEF) in the brain. Here, we review the theoretic basis of qBOLD, as well as existing acquisition and quantification methods. Some published clinical studies are also presented, and the pros and cons of qBOLD method are discussed as well.</p>","PeriodicalId":74435,"journal":{"name":"Phenomics (Cham, Switzerland)","volume":"3 1","pages":"101-118"},"PeriodicalIF":0.0,"publicationDate":"2022-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9883382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9201566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Skin Microbiome, Metabolome and Skin Phenome, from the Perspectives of Skin as an Ecosystem.","authors":"Huizhen Chen,&nbsp;Qi Zhao,&nbsp;Qian Zhong,&nbsp;Cheng Duan,&nbsp;Jean Krutmann,&nbsp;Jiucun Wang,&nbsp;Jingjing Xia","doi":"10.1007/s43657-022-00073-y","DOIUrl":"https://doi.org/10.1007/s43657-022-00073-y","url":null,"abstract":"<p><p>Skin is a complex ecosystem colonized by millions of microorganisms, including bacteria, fungi, and viruses. Skin microbiota is believed to exert critical functions in maintaining host skin health. Profiling the structure of skin microbial community is the first step to overview the ecosystem. However, the community composition is highly individualized and extremely complex. To explore the fundamental factors driving the complexity of the ecosystem, namely the selection pressures, we review the present studies on skin microbiome from the perspectives of ecology. This review summarizes the following: (1) the composition of substances/nutrients in the cutaneous ecological environment that are derived from the host and the environment, highlighting their proposed function on skin microbiota; (2) the features of dominant skin commensals to occupy ecological niches, through self-adaptation and microbe-microbe interactions; (3) how skin microbes, by their structures or bioactive molecules, reshape host skin phenotypes, including skin immunity, maintenance of skin physiology such as pH and hydration, ultraviolet (UV) protection, odor production, and wound healing. This review aims to re-examine the host-microbe interactions from the ecological perspectives and hopefully to give new inspiration to this field.</p>","PeriodicalId":74435,"journal":{"name":"Phenomics (Cham, Switzerland)","volume":"2 6","pages":"363-382"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9712873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9201569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autophagic Clearance of Lipid Droplets Alters Metabolic Phenotypes in a Genetic Obesity-Diabetes Mouse Model.","authors":"Ningxie Chen,&nbsp;Boxun Lu,&nbsp;Yuhua Fu","doi":"10.1007/s43657-022-00080-z","DOIUrl":"10.1007/s43657-022-00080-z","url":null,"abstract":"<p><p>Lipid droplets (LDs) are intracellular organelles that store neutral lipids, and their aberrant accumulation is associated with many diseases including metabolic disorders such as obesity and diabetes. Meanwhile, the potential pathological contributions of LDs in these diseases are unclear, likely due to a lack of chemical biology tools to clear LDs. We recently developed LD-clearance small molecule compounds, Lipid Droplets·AuTophagy TEthering Compounds (LD·ATTECs), that are able to induce autophagic clearance of LDs in cells and in the liver of <i>db/db</i> (C57BL/6J Lepr^db/Lepr^db) mouse model, which is a widely used genetic model for obesity-diabetes. Meanwhile, the potential effects on the metabolic phenotype remain to be elucidated. Here, using the metabolic cage assay and the blood glucose assay, we performed phenotypic characterization of the effects of the autophagic degradation of LDs by LD·ATTECs in the <i>db/db</i> mouse model. The study reveals that LD·ATTECs increased the oxygen uptake of mice and the release of carbon dioxide, enhanced the heat production of animals, partially enhanced the exercise during the dark phase, decreased the blood glucose level and improved insulin sensitivity. Collectively, the study characterized the metabolic phenotypes induced by LD·ATTECs in an obesity-diabetes mouse model, revealing novel functional impacts of autophagic clearance of LDs and providing insights into LD biology and obesity-diabetes pathogenesis from the phenotypic perspective.</p>","PeriodicalId":74435,"journal":{"name":"Phenomics (Cham, Switzerland)","volume":"3 2","pages":"119-129"},"PeriodicalIF":0.0,"publicationDate":"2022-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10110819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9489237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Meta-Analysis of the Genome-Wide Association Studies on Two Genetically Correlated Phenotypes Suggests Four New Risk Loci for Headaches.","authors":"Weihua Meng, Parminder S Reel, Charvi Nangia, Aravind Lathika Rajendrakumar, Harry L Hebert, Qian Guo, Mark J Adams, Hua Zheng, Zen Haut Lu, Debashree Ray, Lesley A Colvin, Colin N A Palmer, Andrew M McIntosh, Blair H Smith","doi":"10.1007/s43657-022-00078-7","DOIUrl":"10.1007/s43657-022-00078-7","url":null,"abstract":"<p><p>Headache is one of the commonest complaints that doctors need to address in clinical settings. The genetic mechanisms of different types of headache are not well understood while it has been suggested that self-reported headache and self-reported migraine were genetically correlated. In this study, we performed a meta-analysis of genome-wide association studies (GWAS) on the self-reported headache phenotype from the UK Biobank and the self-reported migraine phenotype from the 23andMe using the Unified Score-based Association Test (metaUSAT) software for genetically correlated phenotypes (<i>N</i> = 397,385). We identified 38 loci for headaches, of which 34 loci have been reported before and four loci were newly suggested. The <i>LDL receptor related protein 1</i> (<i>LRP1</i>)-<i>Signal Transducer and Activator of Transcription 6</i> (<i>STAT6</i>)-<i>S</i> <i>hort chain</i> <i>D</i> <i>ehydrogenase</i>/<i>R</i> <i>eductase family 9C member 7</i> (<i>SDR9C7</i>) region in chromosome 12 was the most significantly associated locus with a leading <i>p</i> value of 1.24 × 10^-62 of rs11172113. The <i>One Cut homeobox 2</i> (<i>ONECUT2</i>) gene locus in chromosome 18 was the strongest signal among the four new loci with a <i>p</i> value of 1.29 × 10^-9 of rs673939. Our study demonstrated that the genetically correlated phenotypes of self-reported headache and self-reported migraine can be meta-analysed together in theory and in practice to boost study power to identify more variants for headaches. This study has paved way for a large GWAS meta-analysis involving cohorts of different while genetically correlated headache phenotypes.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43657-022-00078-7.</p>","PeriodicalId":74435,"journal":{"name":"Phenomics (Cham, Switzerland)","volume":"3 1","pages":"64-76"},"PeriodicalIF":0.0,"publicationDate":"2022-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9883337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9916267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased Soluble Epoxide Hydrolase Activity Positively Correlates with Mortality in Heart Failure Patients with Preserved Ejection Fraction: Evidence from Metabolomics.","authors":"Liyuan Peng, Ziping Song, Chengcheng Zhao, Kudusi Abuduwufuer, Yanwen Wang, Zheng Wen, Li Ni, Chenze Li, Ying Yu, Yi Zhu, Hualiang Jiang, Jinshan Shen, Xiangrui Jiang, Chen Chen, Xu Zhang, Dao Wen Wang","doi":"10.1007/s43657-022-00069-8","DOIUrl":"10.1007/s43657-022-00069-8","url":null,"abstract":"<p><p>Epoxyeicosatrienoic acids (EETs) have pleiotropic endogenous cardiovascular protective effects and can be hydrolyzed to the corresponding dihydroxyeicosatrienoic acids by soluble epoxide hydrolase (sEH). Heart failure with preserved ejection fraction (HFpEF) has shown an increased prevalence and worse prognosis over the decades. However, the role of sEH activity in HFpEF remains unclear. We enrolled 500 patients with HFpEF and 500 healthy controls between February 2010 and March 2016. Eight types of sEH-related eicosanoids were measured according to target metabolomics, and their correlation with clinical endpoints was also analyzed. The primary endpoint was cardiac mortality, and the secondary endpoint was a composite of cardiac events, including heart failure (HF) readmission, cardiogenic hospitalization, and all-cause mortality. Furthermore, the effect of sEH inhibitors on cardiac diastolic function in HFpEF was investigated in vivo and in vitro. Patients with HFpEF showed significantly enhanced EET degradation by the sEH enzyme compared with healthy controls. More importantly, sEH activity was positively correlated with cardiac mortality in patients with HFpEF, especially in older patients with arrhythmia. A consistent result was obtained in the multiple adjusted models. Decreased sEH activity by the sEH inhibitor showed a significant effective effect on the improvement of cardiac diastolic function by ameliorating lipid disorders in cardiomyocytes of HFpEF mouse model. This study demonstrated that increased sEH activity was associated with cardiac mortality in patients with HFpEF and suggested that sEH inhibition could be a promising therapeutic strategy to improve diastolic cardiac function. Clinical trial identifier: NCT03461107 (https://clinicaltrials.gov).</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43657-022-00069-8.</p>","PeriodicalId":74435,"journal":{"name":"Phenomics (Cham, Switzerland)","volume":"3 1","pages":"34-49"},"PeriodicalIF":0.0,"publicationDate":"2022-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9883375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9147974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adjustment for the Age- and Gender-Related Metabolic Changes Improves the Differential Diagnosis of Parkinsonism.","authors":"Jiaying Lu, Min Wang, Ping Wu, Igor Yakushev, Huiwei Zhang, Sibylle Ziegler, Jiehui Jiang, Stefan Förster, Jian Wang, Markus Schwaiger, Axel Rominger, Sung-Cheng Huang, Fengtao Liu, Chuantao Zuo, Kuangyu Shi","doi":"10.1007/s43657-022-00079-6","DOIUrl":"10.1007/s43657-022-00079-6","url":null,"abstract":"<p><p>Age and gender are the important factors for brain metabolic declines in both normal aging and neurodegeneration, and the confounding effects may influence early and differential diagnosis of neurodegenerative diseases based on the [¹⁸F]fluorodeoxyglucose positron emission tomography ([¹⁸F]FDG PET). We aimed to explore the potential of the adjustment of age- and gender-related confounding factors on [¹⁸F]FDG PET images in differentiation of Parkinson's disease (PD), multiple system atrophy (MSA) and progressive supra-nuclear palsy (PSP). Eight hundred and seventy-seven clinically definitely diagnosed Parkinsonian patients from a benchmark Huashan Parkinsonian PET imaging database were included. An age- and gender-adjusted Z (AGAZ) score was established based on the gender-specific longitudinal metabolic changes on healthy subjects. AGAZ scores and standardized uptake value ratio (SUVR) values were quantified at regional-level and support vector machine-based error-correcting output codes method was applied for classification. Additional references of the classifications based on metabolic pattern scores were included. The feature-based AGAZ score showed the best performance in classification (accuracy for PD, MSA, PSP: 93.1%, 96.3%, 94.8%). In both genders, the AGAZ score consistently achieved the best efficiency, and the improvements compared to the conventional SUVR value for PD, MSA, and PSP mainly laid in specificity (Male: 5.7%; Female: 11.1%), sensitivity (Male: 7.2%; Female: 7.3%), and sensitivity (Male: 7.3%; Female: 17.2%). Female patients benefited more from the adjustment on [¹⁸F]FDG PET in MSA and PSP groups (absolute net reclassification index, <i>p</i> < 0.001). Collectively, the adjustment of age- and gender-related confounding factors may improve the differential diagnosis of Parkinsonism. Particularly, the diagnosis of female Parkinsonian population has the best improvement from this correction.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43657-022-00079-6.</p>","PeriodicalId":74435,"journal":{"name":"Phenomics (Cham, Switzerland)","volume":"3 1","pages":"50-63"},"PeriodicalIF":0.0,"publicationDate":"2022-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9883378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9516053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dopaminergic Dysfunction and Glucose Metabolism Characteristics in Parkin-Induced Early-Onset Parkinson's Disease Compared to Genetically Undetermined Early-Onset Parkinson's Disease.","authors":"Feng-Tao Liu, Jia-Ying Lu, Yi-Min Sun, Ling Li, Yu-Jie Yang, Jue Zhao, Jing-Jie Ge, Ping Wu, Jie-Hui Jiang, Jian-Jun Wu, Chuan-Tao Zuo, Jian Wang","doi":"10.1007/s43657-022-00077-8","DOIUrl":"10.1007/s43657-022-00077-8","url":null,"abstract":"<p><p>While early-onset Parkinson's disease (EOPD) caused by mutations in the parkin gene (<i>PRKN</i>) tends to have a relatively benign course compared to genetically undetermined (GU)-EOPD, the exact underlying mechanisms remain elusive. We aimed to search for the differences between <i>PRKN</i>-EOPD and GU-EOPD by dopamine transporter (DAT) and glucose metabolism positron-emission-tomography (PET) imaging. Twelve patients with <i>PRKN</i>-EOPD and 16 with GU-EOPD who accepted both ¹¹C-2b-carbomethoxy-3b-(4-trimethylstannylphenyl) tropane (¹¹C-CFT) and ¹⁸F-fluorodeoxyglucose PET were enrolled. The ¹¹C-CFT uptake was analyzed on both regional and voxel levels, whereas glucose metabolism was assessed in a voxel-wise fashion. Correlations between DAT and glucose metabolism imaging, DAT imaging and clinical severity, as well as glucose metabolism imaging and clinical severity were explored. Both clinical symptoms and DAT-binding patterns in the posterior putamen were highly symmetrical in patients with <i>PRKN</i>-EOPD, and dopaminergic dysfunction in the ipsilateral putamen was severer in patients with <i>PRKN</i>-EOPD than GU-EOPD. Meanwhile, the DAT binding was associated with the severity of motor dysfunction in  patients with GU-EOPD only. Patients with <i>PRKN</i>-EOPD showed increased glucose metabolism in the contralateral medial frontal gyrus (supplementary motor area (SMA)), contralateral substantia nigra, contralateral thalamus, and contralateral cerebellum. Notably, glucose metabolic activity in the contralateral medial frontal gyrus was inversely associated with regional DAT binding in the bilateral putamen. Patients with <i>PRKN</i>-EOPD showed enhanced metabolic connectivity within the bilateral putamen, ipsilateral paracentral and precentral lobules, and the ipsilateral SMA. Collectively, compared to GU-EOPD, <i>PRKN</i>-EOPD is characterized by symmetrical, more severe dopaminergic dysfunction and relative increased glucose metabolism. Meanwhile, SMA with elevated glucose metabolism and enhanced connectivity may act as compensatory mechanisms in <i>PRKN</i>-EOPD.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43657-022-00077-8.</p>","PeriodicalId":74435,"journal":{"name":"Phenomics (Cham, Switzerland)","volume":"3 1","pages":"22-33"},"PeriodicalIF":0.0,"publicationDate":"2022-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9883374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9201564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chinese Medicine Phenomics (Chinmedphenomics): Personalized, Precise and Promising.","authors":"Chunchun Yuan, Weiqiang Zhang, Jing Wang, Chen Huang, Bing Shu, Qianqian Liang, Tingrui Huang, Jiucun Wang, Qi Shi, Dezhi Tang, Yongjun Wang","doi":"10.1007/s43657-022-00074-x","DOIUrl":"10.1007/s43657-022-00074-x","url":null,"abstract":"<p><p>The systematicness of phenomics and Traditional Chinese Medicine (TCM) enable these two disciplines to interlink with each other. This article discussed the similarity in theory and application between TCM and phenomics and illustrates their respective advantages in diagnosis and treatment of diseases, forming a new discipline eventually. Chinese medicine phenomics (Chinmedphenomics) is built on classic TCM, combined with phenomics technology, and the development of which needs the mega cohort with TCM syndrome and the characteristics of precision medicine as well as multi-disciplinary cooperation, which is personalized, precise and promising, providing unique scientific insights into understanding human health.</p>","PeriodicalId":74435,"journal":{"name":"Phenomics (Cham, Switzerland)","volume":"2 6","pages":"383-388"},"PeriodicalIF":3.7,"publicationDate":"2022-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9712866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9147976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal Association of Cardiac Function by Magnetic Resonance Imaging with Frailty Index: A Mendelian Randomization Study.","authors":"Hui Zhang, Meng Hao, Zixin Hu, Yi Li, Xiaoxi Hu, Xiaoyan Jiang, Zuyun Liu, Xuehui Sun, Xiaofeng Wang","doi":"10.1007/s43657-022-00072-z","DOIUrl":"10.1007/s43657-022-00072-z","url":null,"abstract":"<p><p>Owing to the susceptibility of conventional observational studies to confounding factors and reverse causation, the causal association between cardiac function and frailty is unclear. We aimed to investigate whether cardiac function has causal effects on frailty. In this study, a two-sample Mendelian randomization (MR) study was conducted using genetic variants associated with cardiac function assessed by magnetic resonance imaging phenotypes as instrumental variables. Genetic variants associated with cardiac function by magnetic resonance imaging (including seven cardiac function phenotypes) and the frailty index (FI) were obtained from two large genome-wide association studies. MR estimates from each genetic instrument were combined using inverse variance weighted (IVW), weighted median, and MR‒Egger regression methods. We found that the increase in genetically determined stroke volume (beta - 0.13, 95% CI - 0.16 to - 0.10, <i>p</i> = 1.39E-6), rather than other cardiac phenotypes, was associated with lower FI in MR analysis of IVW after Bonferroni correction. Sensitivity analyses examining potential bias caused by pleiotropy or reverse causality revealed similar findings (e.g., intercept [SE], - 0.008 [0.011], <i>p</i> = 0.47 by MR‒Egger intercept test). The leave-one-out analysis indicated that the association was not driven by single nucleotide polymorphisms. No evidence of heterogeneity was found among the genetic variants (e.g., MR‒Egger: <i>Q</i> statistic = 14.4, <i>p</i> = 0.156). In conclusion, we provided evidence that improved cardiac function could contribute to reducing FI. These findings support the hypothesis that enhancing cardiac function could be an effective prevention strategy for frailty.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43657-022-00072-z.</p>","PeriodicalId":74435,"journal":{"name":"Phenomics (Cham, Switzerland)","volume":"2 6","pages":"430-437"},"PeriodicalIF":0.0,"publicationDate":"2022-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9712899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9500443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}