Genetic correlation and gene-based pleiotropy analysis for four major neurodegenerative diseases with summary statistics

Qiao, Jiahao; Wang, Ting; Shao, Zhonghe; Zhu, Yiliang; Zhang, Meng; Huang, Shuiping; Zeng, Ping

doi:10.1016/j.neurobiolaging.2022.12.012

Cited by 4 publications

(3 citation statements)

References 93 publications

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“…In comparison, 12 out of 45 correlations among neurological diseases reached significance (FDR < 0.05). As recently demonstrated 29,30 , the neurodegenerative disorders ALS, LBD, ALZ and PD formed a cluster of correlated disorders. Additionally, ET was correlated with both PD (rg=0.31, p=1.80x10 -7 ) and MIG (rg=0.17, p=3.90x10 -3 ), FE was correlated with stroke (rg=0.30, p=1.40x10 -3 ), ALS (rg=0.32, p=7.10x10 -3 ) and the other epilepsy subtype GGE (rg=0.61, p=8.04x10 -17 ), while PD was negatively correlated with both MIG (rg=-0.08, p=1.40x10 -2 ) and stroke (rg=-0.10, p=1.57x10 -2 ).…”

Section: Global Genetic Correlationsmentioning

confidence: 59%

“…Genetic overlap has mainly been assessed by estimating pairwise genetic correlations using tools such as linkage disequilibrium (LD) score regression (LDSC) 24 , demonstrating that the genetic risk of psychiatric disorders is highly intercorrelated [25][26][27][28] . On the contrary, there are fewer pairwise genetic correlations among neurological diseases 25,29,30 and between neurological and psychiatric disorders 25,31 . Accordingly, neurological diseases have been considered to be genetically disparate from psychiatric disorders 25 , in line with their clinical distinction 2 .…”

Section: Introductionmentioning

confidence: 99%

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The shared genetic risk architecture of neurological and psychiatric disorders: a genome-wide analysis

Smeland,

Kutrolli,

Bahrami

et al. 2023

Preprint

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Neurological and psychiatric disorders are considered to reflect distinct underlying pathogenic entities. However, the extent to which they share genetic influences remains unclear. Here, we performed a comprehensive analysis of GWAS data, involving nearly 1 million cases across ten neurological diseases and ten psychiatric disorders, to compare their common genetic risk and biological underpinnings. Using complementary statistical tools, we demonstrate extensive genetic overlap across the disorders, with varying degrees of genetic correlations. In particular, migraine, essential tremor, stroke and multiple sclerosis were genetically correlated with several psychiatric disorders. Biological interrogation indicated heterogenous biological processes associated with neurological diseases, while psychiatric disorders consistently implicated neuronal biology. Altogether, the study demonstrates that neurological and psychiatric disorders are not genetically disparate, but share key etiological aspects, which have important implications for disease classification, clinical practice, and genomic precision medicine.

show abstract

Section: Global Genetic Correlationsmentioning

confidence: 59%

Section: Introductionmentioning

confidence: 99%

The shared genetic risk architecture of neurological and psychiatric disorders: a genome-wide analysis

Smeland,

Kutrolli,

Bahrami

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Neurodegenerative diseases (NDs) are late-onset diseases characterized by slow progressive damage to neuronal cells and neuronal loss, disrupting patients’ motor function, cognitive function, and homeostasis [ 1 ]. The incidence of NDs has increased as the population ages worldwide, prompting increased research attention.…”

Section: Introductionmentioning

confidence: 99%

Libertellenone C attenuates oxidative stress and neuroinflammation with the capacity of NLRP3 inhibition

Cao,

Li,

Zhang

et al. 2024

Nat. Prod. Bioprospect.

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Neurodegenerative diseases (NDs) are common chronic diseases arising from progressive damage to the nervous system. Here, in-house natural product database screening revealed that libertellenone C (LC) obtained from the fermentation products of Arthrinium arundinis separated from the gut of a centipede collected in our Tongji campus, showed a remarkable neuroprotective effect. Further investigation was conducted to clarify the specific mechanism. LC dose-dependently reversed glutamate-induced decreased viability, accumulated reactive oxygen species, mitochondrial membrane potential loss, and apoptosis in SH-SY5Y cells. Network pharmacology analysis predicted that the targets of LC were most likely directly related to oxidative stress and the regulation of inflammatory factor-associated signaling pathways. Further study demonstrated that LC attenuated nitrite, TNF-α, and IL-1β production and decreased inducible nitric oxide synthase and cyclooxygenase expression in lipopolysaccharide-induced BV-2 cells. LC could directly inhibit NLRP3 inflammasome activation by decreasing the expression levels of NLRP3, ASC, cleaved Caspase-1, and NF-κB p65. Our results provide a new understanding of how LC inhibits the NLRP3 inflammasome in microglia, providing neuroprotection. These findings might guide the development of effective LC-based therapeutic strategies for NDs.

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Identifying risk loci for FTD and shared genetic component with ALS: A large-scale multitrait association analysis

Chen,

Gao,

Liu

et al. 2024

Neurobiology of Aging

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Genetic correlation and gene-based pleiotropy analysis for four major neurodegenerative diseases with summary statistics

Cited by 4 publications

References 93 publications

The shared genetic risk architecture of neurological and psychiatric disorders: a genome-wide analysis

The shared genetic risk architecture of neurological and psychiatric disorders: a genome-wide analysis

Libertellenone C attenuates oxidative stress and neuroinflammation with the capacity of NLRP3 inhibition

Identifying risk loci for FTD and shared genetic component with ALS: A large-scale multitrait association analysis

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