Gene-gene Interaction Analysis by IAC (Interaction Analysis by Chi-Square) - A Novel Biological Constraint-based Interaction Analysis Framework

Author(s):  
Sidney K. Chu ◽  
Samuel Guanglin Xu ◽  
Feng Xu ◽  
Nelson L. S. Tang
Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 1056
Author(s):  
Katarzyna Leźnicka ◽  
Ewelina Żyźniewska-Banaszak ◽  
Magdalena Gębska ◽  
Anna Machoy-Mokrzyńska ◽  
Anna Krajewska-Pędzik ◽  
...  

The COL1A1 and COL5A1 variants have been associated with the risk of musculoskeletal injuries. Therefore, the main aim of the study was to investigate the association between three polymorphisms within two genes (rs1800012 in COL1A1, as well as rs12722 and rs13946 in COL5A1) and the reported, yet rarely described in the literature, injuries of the joint and muscle area in a physically active Caucasian population. Polish students (n = 114) were recruited and divided into the following two groups: students with (n = 53) and without (n = 61) injures. Genotyping was carried out using real-time PCR. The results obtained revealed a statistically significant association between rs1800012 COL1A1 and injury under an overdominant model. Specifically, when adjusted for age and sex, the GT heterozygotes had a 2.2 times higher chance of being injured compared with both homozygotes (TT and GG, 95% CI 0.59–5.07, p = 0.040). However, no significant interaction between the COL5A1 variants, either individually or in haplotype combination, and susceptibility to injury were found. In addition, the gene–gene interaction analysis did not reveal important relationships with the musculoskeletal injury status. It was demonstrated that rs1800012 COL1A1 may be positively associated with physical activity-related injuries in a Caucasian population. Harboring the specific GT genotype may be linked to a higher risk of being injured.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhiying Chen ◽  
Jiahui Wei ◽  
Min Li ◽  
Yongjuan Zhao

Abstract Background This study aimed to identify potential circular ribonucleic acid (circRNA) signatures involved in the pathogenesis of early-stage lung adenocarcinoma (LAC). Methods The circRNA sequencing dataset of early-stage LAC was downloaded from the Gene Expression Omnibus database. First, the differentially expressed circRNAs (DEcircRNAs) between tumour and non-tumour tissues were screened. Then, the corresponding miRNAs and their target genes were predicted. In addition, prognosis-related genes were identified using survival analysis and further used to build a network of competitive endogenous RNAs (ceRNAs; DEcircRNA–miRNA–mRNA). Finally, the functional analysis and drug–gene interaction analysis of mRNAs in the ceRNA network was performed. Results A total of 35 DEcircRNAs (30 up-regulated and 5 down-regulated circRNAs) were identified. Moreover, 135 DEcircRNA–miRNA and 674 miRNA–mRNA pairs were predicted. The survival analysis of these target mRNAs revealed that 60 genes were significantly associated with survival outcomes in early-stage LAC. Of these, high levels of PSMA 5 and low levels of NAMPT, CPT 2 and TNFSF11 exhibited favourable prognoses. In addition, the DEcircRNA–miRNA–mRNA network was constructed, containing 5 miRNA–circRNA (hsa_circ_0092283/hsa-miR-762/hsa-miR-4685-5p; hsa_circ_0070610/hsa-let-7a-2-3p/hsa-miR-3622a-3p; hsa_circ_0062682/hsa-miR-4268) and 60 miRNA–mRNA pairs. Functional analysis of the genes in the ceRNA network showed that they were primarily enriched in the Wnt signalling pathway. Moreover, PSMA 5, NAMPT, CPT 2 and TNFSF11 had strong correlations with different drugs. Conclusion Three circRNAs (hsa_circ_0062682, hsa_circ_0092283 and hsa_circ_0070610) might be potential novel targets for the diagnosis of early-stage LAC.


2021 ◽  
Vol 3 ◽  
Author(s):  
Nuno Leite ◽  
Jorge Arede ◽  
Ximing Shang ◽  
Julio Calleja-González ◽  
Alberto Lorenzo

The aims of this study were two-fold: (1) to inspect separately for the relative age and birthplace effects for players selected in the National Basketball Association (NBA) draft; (2) to explore the interaction among these factors and analyse this interaction in players' career performance. The database was obtained from the official records of the players (n = 1,738), who were selected during the annual editions of the NBA Draft from 1990 to 2019. The participants' date of birth was analyzed according to the month of birth and divided into four quartiles. The place of birth was compared to the distribution of the general population' places of birth based on different communities' sizes. Chi-square analysis were used to determine if the relative age and birthplace of the players drafted differed in any systematic way from official census population distributions. Cluster analysis and standardized residuals were calculated to analyse the interaction among the contextual factors and the players' career performance. The data revealed that early-born players (Q1 and Q2) were over-represented. Moreover, players born in smaller cities (<100,000) were over-represented. The interaction analysis revealed that the players born in the bigger communities relate mainly with relatively younger players, and clusters that correspond to players born in smaller communities integrated the relatively older players. No differences were found in the players' career performance. Researchers, coaches and practitioners should be aware of the interaction between contextual factors to help nurture the development of sport talent regardless of age-related issues or communities' size.


2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Yong-Ling He ◽  
Jun Yang ◽  
Zhi-Neng Zeng ◽  
Xiang Shi

Introduction. A previous work has discovered that chromosome 1q32 locus linked to the risk of systemic lupus erythematosus (SLE) and miR-181b located on the susceptibility site with downregulation inversely correlating to its target molecular interferon alpha 1 (IFNA1). The purpose of this study was to investigate the association of miR-181b and IFNA1 polymorphisms with IS risk. Methods. The miR-181b rs322931, IFNA1 rs1332190, and rs10811543 were genotyped using a Multiplex SNaPshot assay. miR-181b expression levels in plasma of SLE patients and controls were analyzed using quantitative PCR. Results. The rs322931 CT, CT/TT, and T allele exerted an increased trend of SLE risk (CT vs. CC: adjusted OR=1.71, 95% CI 1.16-2.50, P=0.01; CT/TT vs. CC: adjusted OR=1.45, 95% CI 1.08-1.95, P=0.01; T vs. C: adjusted OR=1.38, 95% CI 1.07-1.79, P=0.01). Combined genotypes of the rs322931 CT/TT+rs1332190 TT and the rs322931 CC+rs10811543 AG/AA also revealed an increased risk of SLE. Gene-gene interaction analysis showed that a three-locus model consisting of rs322931, rs1332190, and rs10811543 attributed an increased risk of SLE. Further genotype-phenotype analysis revealed that rs322931 CT/TT carriers displayed lower levels of miR-181b. Conclusions. These findings indicate that the miR-181b rs322931 may be singly and jointly responsible for the etiology of SLE by altering miR-181b expression.


2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Ying Meng ◽  
Susan Groth ◽  
Jill R. Quinn ◽  
John Bisognano ◽  
Tong Tong Wu

Hypertension tends to perpetuate in families and the heritability of hypertension is estimated to be around 20–60%. So far, the main proportion of this heritability has not been found by single-locus genome-wide association studies. Therefore, the current study explored gene-gene interactions that have the potential to partially fill in the missing heritability. A two-stage discovery-confirmatory analysis was carried out in the Framingham Heart Study cohorts. The first stage was an exhaustive pairwise search performed in 2320 early-onset hypertensive cases with matched normotensive controls from the offspring cohort. Then, identified gene-gene interactions were assessed in an independent set of 694 subjects from the original cohort. Four unique gene-gene interactions were found to be related to hypertension. Three detected genes were recognized by previous studies, and the other 5 loci/genes (MAN1A1, LMO3, NPAP1/SNRPN, DNAL4, and RNA5SP455/KRT8P5) were novel findings, which had no strong main effect on hypertension and could not be easily identified by single-locus genome-wide studies. Also, by including the identified gene-gene interactions, more variance was explained in hypertension. Overall, our study provides evidence that the genome-wide gene-gene interaction analysis has the possibility to identify new susceptibility genes, which can provide more insights into the genetic background of blood pressure regulation.


PLoS ONE ◽  
2013 ◽  
Vol 8 (4) ◽  
pp. e61943 ◽  
Author(s):  
Zhixiang Zhu ◽  
Xiaoran Tong ◽  
Zhihong Zhu ◽  
Meimei Liang ◽  
Wenyan Cui ◽  
...  

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