SNP-SNP interactions between WNT4 and WNT5A were associated with obesity related traits in Han Chinese Population

Dong, Shanshan; Hu, Weixin; Yang, Tie‐Lin; Chen, Xiaofeng; Yan, Han; Chen, Xiang-Ding; Tan, Lijun; Tian, Qing; Deng, Hong‐Wen; Guo, Yan

doi:10.1038/srep43939

Cited by 12 publications

(10 citation statements)

References 39 publications

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“…To date, fewer studies have examined the effects of interactions on obesity. Despite this, some obesity-related interactions still have been found, including PRKD1 - FTO and WNT4 - WNT5A (Wei et al, 2012; Young et al, 2016; Dong et al, 2017). Pathway-based analysis is an alternative approach to detect gene interactions.…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Interaction and Pathway Association Studies for Body Mass Index

et al. 2019

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Objective: We investigated gene interactions (epistasis) for body mass index (BMI) in a European-American adult female cohort via genome-wide interaction analyses (GWIA) and pathway association analyses. Methods: Genome-wide pairwise interaction analyses were carried out for BMI in 493 extremely obese cases (BMI > 35 kg/m 2 ) and 537 never-overweight controls (BMI < 25 kg/m 2 ). To further validate the results, specific SNPs were selected based on the GWIA results for haplotype-based association studies. Pathway-based association analyses were performed using a modified Gene Set Enrichment Algorithm (GSEA) (GenGen program) to further explore BMI-related pathways using our genome wide association study (GWAS) data set, GIANT, ENGAGE, and DIAGRAM Consortia. Results: The EXOC4 -1q23.1 interaction was associated with BMI, with the most significant epistasis between rs7800006 and rs10797020 ( P = 2.63 × 10 -11 ). In the pathway-based association analysis, Tob1 pathway showed the most significant association with BMI (empirical P < 0.001, FDR = 0.044, FWER = 0.040). These findings were further validated in different populations. Conclusion: Genome-wide pairwise SNP-SNP interaction and pathway analyses suggest that EXOC4 and TOB1-related pathways may contribute to the development of obesity.

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Section: Discussionmentioning

confidence: 99%

Genome-Wide Interaction and Pathway Association Studies for Body Mass Index

et al. 2019

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“…There are two studies showing that SNPs of the Wnt4 gene can affect its expression and function. SNP rs7521902 in Wnt4 is significantly correlated with the pathogenesis of endometriosis (Angioni et al, 2020), and rs2072920 in Wnt4 is associated with body mass index (BMI) variations in the Han Chinese population (Dong et al, 2017). We identified the critical regions of the Wnt4 promoter which contained a SNP -3015 (G > C) and we showed that SNP -3015 (G > C) in the Wnt4 gene was significantly associated with keel length and comb length in chickens, the individuals with CG genotype having a longer keel length.…”

Section: Discussionmentioning

confidence: 99%

Key Promoter Region of Wnt4 response to FSH and Genetic Effect on Several Production Traits of Its Mutations in Chicken

Zhong

Wang

Liu³

et al. 2021

Preprint

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The signaling pathway of the wingless-type mouse mammary tumor virus integration site (Wnt) plays an important role in ovarian and follicular development. Wnt4 was shown in our previous study to be involved in the selection and development of chicken follicles by up-regulating the expression of follicle stimulating hormone receptors (FSHR), stimulating the proliferation of follicular granulosa cells and increasing the secretion of steroidal hormones. To further characterize cis-elements regulating chicken Wnt4 transcription, in this study we determined critical regulatory regions affecting chicken Wnt4 transcription, then identified a single nucleotide polymorphism (SNP) in this region, and finally analyzed the association of the SNP with chicken production traits. The results showed that the 5 regulatory region from -3354 to -2689 of the chicken Wnt4 gene had the strongest activity and greatest response to FSH stimulation, and that one SNP site -3015 (G > C) in this segment was identified as affecting the binding of NFAT5 (nuclear factor of activated T cells 5). When G was replaced by C at this site, it eliminated the binding by NFAT5. Moreover, this locus was significantly associated with the keel length and comb length of hens. Individuals with the genotype CG had longer keels while those with genotype CC had longer combs. Collectively, these data suggested that the SNP-3015 (G > C) is (i) involved in the regulation of Wnt4 gene expression by affecting the binding of NFAT5, (ii) associated with chicken keel length and comb length, and (iii) is a potential DNA marker in the molecular breeding of chickens for egg laying.

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“…Based on the results, we speculated that the interaction of rs807181 and 807183 affected the ATG4A gene and down-regulated or inhibited its role in autophagy, which led to an increased susceptibility and ability of HPV to bind to the host. Some studies have shown that SNP-SNP interactions were notably associated with BMI ( 30 , 31 ), as well as colon cancer. The association between ATG4A genetic variations and HPV infection is still unknown.…”

Section: Discussionmentioning

confidence: 99%

Nucleotide variation in ATG4A and susceptibility to cervical cancer in Southwestern Chinese women

Mao

Wang

et al. 2017

Oncol Lett

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Early detection of human papillomavirus (HPV) is important for the clinical diagnosis of cervical cancer. However, to date, the pathogenesis of cervical cancer is still unclear. Autophagy is a dynamic process that contributes to the maintenance of cellular homeostasis. Here, we investigate whether variants of autophagy genes affect the occurrence of cervical cancer. In this study, our results indicate that single nucleotide polymorphisms (SNPs) of autophagy-related protein 4 (ATG4), including rs4036579, rs5973822, rs807181, rs807182 and rs807183, have a significant relationship with cervical cancer risk. Furthermore, stratified analysis suggests that the homozygous variant genotype could decrease the risk of cervical cancer and should be considered when investigating the role of HPV in cervical cancer. We aim to investigate whether SNPs of ATG4A contribute to HPV infection in the population of Southwestern China. The association of both single SNPs and SNP-SNP interactions with HPV was evaluated in a sample of cancer cases and healthy control subjects. The interaction of rs807181 and rs807183 was associated with HPV infection in case and control subjects (combined P=2.00×10−3 and 3.22×10−2, respectively). This result showed that ATG4A SNP interactions may affect HPV infection in the population of Southwestern China. Notably, the autophagy gene ATG4A may contribute to cervical cancer.

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SNP-SNP interactions between WNT4 and WNT5A were associated with obesity related traits in Han Chinese Population

Cited by 12 publications

References 39 publications

Genome-Wide Interaction and Pathway Association Studies for Body Mass Index

Genome-Wide Interaction and Pathway Association Studies for Body Mass Index

Key Promoter Region of Wnt4 response to FSH and Genetic Effect on Several Production Traits of Its Mutations in Chicken

Nucleotide variation in ATG4A and susceptibility to cervical cancer in Southwestern Chinese women

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