Genetic determinants of daytime napping and effects on cardiometabolic health

Dashti, Hassan S.; Daghlas, Iyas; Lane, Jacqueline M.; Huang, Yaoguo; Udler, Miriam S.; Wang, Heming; Ollila, Hanna; Jones, Samuel E.; Kim, Jaegil; Wood, Andrew R.; Agee, Michelle; Auton, Adam; Bell, Robert K.; Bryc, Katarzyna; Clark, Sarah; Elson, Sarah L.; Fletez-Brant, Kipper; Fontanillas, Pierre; Furlotte, Nicholas A.; Gandhi, Pooja; Heilbron, Karl; Hicks, Barry; Hinds, David A.; Huber, Karen E.; Jewett, Ethan M.; Jiang, Yunxuan; Kleinman, Aaron; Lin, Keng-Han; Litterman, Nadia K.; Luff, Marie K.; McCreight, Jennifer C.; McIntyre, Matthew H.; McManus, Kimberly F.; Mountain, Joanna L.; Mozaffari, Sahar V.; Nandakumar, Priyanka; Noblin, Elizabeth S.; Northover, Carrie A. M.; O’Connell, Jared; Petrakovitz, Aaron A.; Pitts, Steven J.; Poznik, G. David; Sathirapongsasuti, J. Fah; Shastri, Anjali J.; Shelton, Janie F.; Shringarpure, Suyash; Tian, Chao; Tung, Joyce Y.; Tunney, Robert J.; Vacic, Vladimir; Wang, Xin; Zare, Amir S.; Weedon, Michael N.; Aslibekyan, Stella; Garaulet, Marta; Saxena, Richa

doi:10.1038/s41467-020-20585-3

Cited by 180 publications

(107 citation statements)

References 112 publications

(181 reference statements)

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“…A study using bioinformatics and transgenic mice approaches indicated the regulatory role of MEIS1 in neuropeptide substance p expression in the amygdala, suggesting a mechanism underlying anxiety and depression [42]. Second, the RP11-6N13.1 locus has been implicated in early sleep timing [43] and how it contributes to insomnia remains to be determined. In addition to our finding of rs126580832, rs40465 near RP11-6N13.1 has been reported to be associated with broad depression [15].…”

Section: Discussionmentioning

confidence: 99%

GWAS Meta-Analysis Reveals Shared Genes and Biological Pathways between Major Depressive Disorder and Insomnia

Lin

Wang

Chen

2021

Genes

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Major depressive disorder (MDD) is one of the most prevalent and disabling mental disorders worldwide. Among the symptoms of MDD, sleep disturbance such as insomnia is prominent, and the first reason patients may seek professional help. However, the underlying pathophysiology of this comorbidity is still elusive. Recently, genome-wide association studies (GWAS) have begun to unveil the genetic background of several psychiatric disorders, including MDD and insomnia. Identifying the shared genomic risk loci between comorbid psychiatric disorders could be a valuable strategy to understanding their comorbidity. This study seeks to identify the shared genes and biological pathways between MDD and insomnia based on their shared genetic variants. First, we performed a meta-analysis based on the GWAS summary statistics of MDD and insomnia obtained from Psychiatric Genomics Consortium and UK Biobank, respectively. Next, we associated shared genetic variants to genes using two gene mapping strategies: (a) positional mapping based on genomic proximity and (b) expression quantitative trait loci (eQTL) mapping based on gene expression linkage across multiple tissues. As a result, a total of 719 shared genes were identified. Over half (51%) of them are protein-coding genes. Functional enrichment analysis shows that the most enriched biological pathways are related to epigenetic modification, sensory perception, and immunologic signatures. We also identified druggable targets using a network approach. Together, these results may provide insights into understanding the genetic predisposition and underlying biological pathways of comorbid MDD and insomnia symptoms.

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Section: Discussionmentioning

confidence: 99%

GWAS Meta-Analysis Reveals Shared Genes and Biological Pathways between Major Depressive Disorder and Insomnia

Lin

Wang

Chen

2021

Genes

View full text Add to dashboard Cite

show abstract

“…A study using bioinformatics and transgenic mice approaches indicated the regulatory role of MEIS1 in neuropeptide substance P expression in the amygdala, suggesting a mechanism underlying anxiety and depression [42]. Second, the RP11-6N13.1 locus has been implicated in early sleep timing [43] and how it contributes to insomnia remains to be determined. Besides our finding of rs126580832, rs40465 near RP11-6N13.1 has been reported to be associated with broad depression [15].…”

Section: Discussionmentioning

confidence: 99%

GWAS Meta-Analysis Reveals Shared Genes and Biological Pathways Between Major Depressive Disorder and Insomnia

Lin¹,

Wang²,

Chen³

2021

Preprint

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Major depressive disorder (MDD) is one of the most prevalent and disabling mental disorders worldwide. Among the symptoms of MDD, sleep disturbance such as insomnia is prominent and the first reason patients may seek professional help. However, the underlying pathophysiology of this comorbidity is still elusive. Recently, genome-wide association studies (GWAS) have begun to unveil the genetic background of several psychiatric disorders, including MDD and insomnia. Identifying the shared genomic risk loci between comorbid psychiatric disorders could be a valuable strategy to understand their comorbidity. This study seeks to identify the shared genes and biological pathways between MDD and insomnia based on their shared genetic variants. First, we performed a meta-analysis based on the GWAS summary statistics of MDD and insomnia obtained from Psychiatric Genomics Consortium and UK Biobank, respectively. Next, we associated shared genetic variants to genes using two gene mapping strategies: (a) positional mapping based on genomic proximity and (b) expression quantitative trait loci (eQTL) mapping based on gene expression linkage across multiple tissues. As a result, a total of 719 shared genes were identified. Over half (51%) of them are protein-coding genes. Functional enrichment analysis shows that the most enriched biological pathways are related to epigenetic modification, sensory perception, and immunologic signatures. We also identified druggable targets using a network approach. Together these results may provide insights into understanding the genetic predisposition and underlying biological pathways of comorbid MDD and insomnia symptoms.

show abstract

“…A recent study based on UK Biobank has revealed the positive association between FADS1 with rs174561 variant in the frontal cortex and daytime napping. Moreover, two-sample Mendelian randomization analyses have confirmed that more frequent daytime napping is correlating to independent risk factors (waist circumference and blood pressure) of cardiometabolic diseases [24] . Given the fact that many downstream inflammatory mediators are generated by the D5D-catalyzed n-6 PUFAs pathway, the correlation between daytime napping and cardiometabolic risks may be explained by activation of AA/PGs-mediated inflammatory response.…”

Section: D5d Implication In Pufa Related Diseases Including Cancermentioning

confidence: 95%

Delta-5-desaturase: A novel therapeutic target for cancer management

Pang

Shah

et al. 2021

Translational Oncology

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Highlights D5D is an independent prognostic factor in cancer. D5D aggravates cancer progression via mediating AA/PGE 2 production from DGLA. AA/PGE 2 promotes cancer progression via regulating the tumor microenvironment. Inhibition of D5D redirects COX-2 catalyzed DGLA peroxidation, producing 8-HOA. 8-HOA suppress cancer by regulating proliferation, apoptosis, and metastasis.

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Genetic determinants of daytime napping and effects on cardiometabolic health

Cited by 180 publications

References 112 publications

GWAS Meta-Analysis Reveals Shared Genes and Biological Pathways between Major Depressive Disorder and Insomnia

GWAS Meta-Analysis Reveals Shared Genes and Biological Pathways between Major Depressive Disorder and Insomnia

GWAS Meta-Analysis Reveals Shared Genes and Biological Pathways Between Major Depressive Disorder and Insomnia

Delta-5-desaturase: A novel therapeutic target for cancer management

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