A variant within <i>FGF1</i> is associated with Alzheimer's disease in the Han Chinese population

Tao, Qing‐Qing; Sun, Yi‐Min; Liu, Zhijun; Wang, Ni; Yang, Ping; Li, Honglei; Lu, Shen-Ji; Wu, Zhi‐Ying

doi:10.1002/ajmg.b.32205

Cited by 13 publications

(16 citation statements)

References 27 publications

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“…In addition to our findings, dysregulation of H4K12 acetylation is involved in age-associated memory loss (Peleg et al, 2010). FGF1 may be involved in the pathophysiology of Alzheimer’s disease (Lou et al, 2012; Tao et al, 2014; Yamagata et al, 2004) and recombinant FGFs have been used to treat multiple disorders (Beenken and Mohammadi, 2009). Therefore, Fgf1b and the components of its transcriptional machinery may be a target for cognitive enhancement therapy.…”

Section: Discussionmentioning

confidence: 99%

CRTC1 Nuclear Translocation Following Learning Modulates Memory Strength via Exchange of Chromatin Remodeling Complexes on the Fgf1 Gene

et al. 2017

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SUMMARY Memory is formed by synapse-to-nucleus communication that leads to regulation of gene transcription, but the identity and organizational logic of signaling pathways involved in this communication remain unclear. Here we find that the transcription factor CRTC1 is a critical determinant of sustained gene transcription and memory strength in the hippocampus. Following associative learning, synaptically localized CRTC1 is translocated to the nucleus and regulates Fgf1b transcription in an activity-dependent manner. After both weak and strong training, the HDAC3–N-CoR corepressor complex leaves the Fgf1b promoter and a complex involving the translocated CRTC1, phosphorylated CREB and histone acetyltransferase CBP induces transient transcription. Strong training later substitutes KAT5 for CBP, a process that is dependent on CRTC1, but not on CREB phosphorylation. This in turn leads to long-lasting Fgf1b transcription and memory enhancement. Thus, memory strength relies on activity-dependent changes in chromatin and temporal regulation of gene transcription on specific CREB/CRTC1 gene targets.

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Section: Discussionmentioning

confidence: 99%

CRTC1 Nuclear Translocation Following Learning Modulates Memory Strength via Exchange of Chromatin Remodeling Complexes on the Fgf1 Gene

et al. 2017

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“…FGF‐1 promotes the survival of neurons, and it was reported that serum FGF‐1 in patients with AD was higher than in patients without AD . It was also reported that variants within FGF‐1 were associated with AD in Chinese Han population . The ADRA1A gene located on chromosome 8 has been selected 15%, and only the additive effects have been selected.…”

Section: Real‐data Applicationmentioning

confidence: 99%

“…50 It was also reported that variants within FGF-1 were associated with AD in Chinese Han population. 51 The ADRA1A gene located on chromosome 8 has been selected 15%, and only the additive effects have been selected. It has been shown that mutations in ADRA1A can lead to early onset of AD.…”

Section: Accuracy Comparisons For Fdgmentioning

confidence: 99%

Multikernel linear mixed model with adaptive lasso for complex phenotype prediction

Wen

2020

Statistics in Medicine

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Linear mixed models (LMMs) and their extensions have been widely used for high‐dimensional genomic data analyses. While LMMs hold great promise for risk prediction research, the high dimensionality of the data and different effect sizes of genomic regions bring great analytical and computational challenges. In this work, we present a multikernel linear mixed model with adaptive lasso (KLMM‐AL) to predict phenotypes using high‐dimensional genomic data. We develop two algorithms for estimating parameters from our model and also establish the asymptotic properties of LMM with adaptive lasso when only one dependent observation is available. The proposed KLMM‐AL can account for heterogeneous effect sizes from different genomic regions, capture both additive and nonadditive genetic effects, and adaptively and efficiently select predictive genomic regions and their corresponding effects. Through simulation studies, we demonstrate that KLMM‐AL outperforms most of existing methods. Moreover, KLMM‐AL achieves high sensitivity and specificity of selecting predictive genomic regions. KLMM‐AL is further illustrated by an application to the sequencing dataset obtained from the Alzheimer's disease neuroimaging initiative.

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“…In addition to CRTC1, there are also reports suggesting a possible role of FGF1 in Alzheimer’s disease. Genetic studies indicate significant association of single nucleotide polymorphisms (SNPs) within the FGF1 gene (Tao et al, 2014; Yamagata et al, 2004). In addition, the number of FGF1-immunolabeled neurons is reduced in patients with Alzheimer’s disease (Thorns et al, 2001; Thorns and Masliah, 1999).…”

Section: Possible Involvement Of Crtc1 and Fgf1 In Memory-related Dismentioning

confidence: 99%

Epigenetic regulation of Fgf1 transcription by CRTC1 and memory enhancement

Uchida

Shumyatsky

2018

Brain Research Bulletin

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Recent evidence demonstrates that epigenetic regulation of gene transcription is critically involved in learning and memory. Here, we discuss the role of histone acetylation and DNA methylation, which are two best understood epigenetic processes in memory processes. More specifically, we focus on learning-strength-dependent changes in chromatin on the fibroblast growth factor 1 (Fgf1) gene and on the molecular events that modulate regulation of Fgf1 transcription, required for memory enhancement, with the specific focus on CREB-regulated transcription coactivator 1 (CRTC1).

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A variant within FGF1 is associated with Alzheimer's disease in the Han Chinese population

Cited by 13 publications

References 27 publications

CRTC1 Nuclear Translocation Following Learning Modulates Memory Strength via Exchange of Chromatin Remodeling Complexes on the Fgf1 Gene

CRTC1 Nuclear Translocation Following Learning Modulates Memory Strength via Exchange of Chromatin Remodeling Complexes on the Fgf1 Gene

Multikernel linear mixed model with adaptive lasso for complex phenotype prediction

Epigenetic regulation of Fgf1 transcription by CRTC1 and memory enhancement

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