Allele Model Research Articles

A breed-of-origin of alleles model that includes crossbred data improves predictive ability for crossbred animals in a multi-breed population

BackgroundRecently, crossbred animals have begun to be used as parents in the next generations of dairy and beef cattle systems, which has increased the interest in predicting the genetic merit of those animals. The primary objective of this study was to investigate three available methods for genomic prediction of crossbred animals. In the first two methods, SNP effects from within-breed evaluations are used by weighting them by the average breed proportions across the genome (BPM method) or by their breed-of-origin (BOM method). The third method differs from the BOM in that it estimates breed-specific SNP effects using purebred and crossbred data, considering the breed-of-origin of alleles (BOA method). For within-breed evaluations, and thus for BPM and BOM, 5948 Charolais, 6771 Limousin and 7552 Others (a combined population of other breeds) were used to estimate SNP effects separately within each breed. For the BOA, the purebreds' data were enhanced with data from ~ 4K, ~ 8K or ~ 18K crossbred animals. For each animal, its predictor of genetic merit (PGM) was estimated by considering the breed-specific SNP effects. Predictive ability and absence of bias were estimated for crossbreds and the Limousin and Charolais animals. Predictive ability was measured as the correlation between PGM and the adjusted phenotype, while the regression of the adjusted phenotype on PGM was estimated as a measure of bias.ResultsWith BPM and BOM, the predictive abilities for crossbreds were 0.468 and 0.472, respectively, and with the BOA method, they ranged from 0.490 to 0.510. The performance of the BOA method improved as the number of crossbred animals in the reference increased and with the use of the correlated approach, in which the correlation of SNP effects across the genome of the different breeds was considered. The slopes of regression for PGM on adjusted phenotypes for crossbreds showed overdispersion of the genetic merits for all methods but this bias tended to be reduced by the use of the BOA method and by increasing the number of crossbred animals.ConclusionsFor the estimation of the genetic merit of crossbred animals, the results from this study suggest that the BOA method that accommodates crossbred data can yield more accurate predictions than the methods that use SNP effects from separate within-breed evaluations.

PADI4 and IL-33 gene polymorphisms with susceptibility to systemic lupus erythematosus and juvenile idiopathic arthritis, a systematic review and meta-analysis.

This study evaluated the association between peptidyl arginine deiminase type IV (PADI4) and interleukin 33 (IL-33) with systemic lupus erythematosus (SLE) and juvenile idiopathic arthritis (JIA). We searched the PubMed, Web of Science, Embase and Cochrane Library databases to retrieve articles published up to January 20, 2023. Stata/SE 17.0 (College Station, TX) software was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). The cohort study, case-control study focusing on the PADI4, IL-33 polymorphism, and SLE, JIA were retrieved. The data included basic information of each study and the genotypes and allele frequencies. Studies in PADI4 rs2240340 = 2 and 3 IL-33(rs1891385 = 3, rs10975498 = 2, rs1929992 = 4) were found in 6 articles. Overall, only the IL-33 rs1891385 show significant association between SLE in all 5 models. The results were OR (95% CI) = 1.528 (1.312, 1.778), P = .000 in Allele model (C vs A), OR (95% CI) =1.473 (1.092, 1.988), P = .000 in Dominant model (CC + CA vs AA), 2.302 (1.583, 3.349), P = .000 in Recessive model (CC vs CA + AA), 2.711 (1.845, 3.983), P = .000 in Homozygote model (CC vs AA), 5.568 (3.943, 7.863), P = .000 in Heterozygote model (CA vs AA). PADI4 rs2240340, IL-33 rs10975498, IL-33 rs1929992 were not found to be association with the risk of SLE and JIA. In gene model, statistically significant association was found between IL-33 rs1891385 and SLE in sensitivity analysis. Egger's publication bias plot showed there was no publication bias (P = .165). Only in recessive model the heterogeneity test was significant (I2 = 57.9%, P ≤ .093) of IL-33 rs1891385. The current study suggests that in all 5 model, IL-33 rs1891385 polymorphism may be associated with genetic susceptibility to SLE. There was unclear association found between PADI4 rs2240340, IL-33 rs10975498, and IL-33 rs1929992 polymorphisms and SLE and JIA. Due to the limitations of included studies and the risk of heterogeneity, additional research is required to confirm our findings. CRD42023391268.

Polymorphism rs1057147 located in mesothelin gene predicts lymph node metastasis in patients with gastric cancer

Lymph node metastasis, a crucial factor in the spread of gastric cancer (GC), is strongly associated with a negative prognosis for patients. This study aimed to investigate the association of the mesothelin (MSLN) gene polymorphisms (rs3764247, rs3764246, rs12597489, rs1057147, and rs3765319) with the risk of lymph node metastasis of GC patients in a Chinese Han population. The PCR-LDR genotyping was used to detect the genotypes of MSLN polymorphisms in GC patients with lymph node metastasis (n = 610) or without (n = 356). Our research indicates that certain genetic markers, specifically rs3764247, rs3764246, rs12597489, and rs3765319, do not appear to be linked with an increased risk of lymph node metastasis in GC. However, we did observe that patients with the rs1057147 GA genotype exhibited a higher likelihood of lymph node metastasis in GC when compared to those with the GG genotype (OR = 1.33, 95% CI = 1.01 - 1.76, P= 0.045). Patients with rs1057147 GA + AA genotype were found to have a higher likelihood of lymph node involvement (OR = 1.35, 95% CI = 1.03 - 1.77, P = 0.029) when compared to those with GG genotype in the dominant model. The allelic model revealed that the A allele of rs1057147 exhibited a stronger correlation with lymph node metastasis compared to the G allele (OR = 1.28, 95% CI = 1.02 - 1.60, P = 0.031). In addition, we found that rs1057147 polymorphism revealed a poor prognosis for GC patients with lymph node metastasis. Further stratified analysis revealed that the prognostic effect of rs1057147 was more pronounced in patients with GC who had lymph node metastasis and had a tumor size of 4cm or greater, as well as more than 2 lymph node metastases. Bioinformatics studies showed that the binding mode of miR-3144-5p or miR-3619-3p to MSLN was altered by the mutation of rs1057147. Our study confirmed the important role of MSLN rs1057147 polymorphism locus in GC lymph node metastases and suggested a potential prognostic factor during GC progression. KEY POINTS: • Rs1057147 GA genotype had an increased risk of lymph node metastasis in gastric cancer. • The A allele of rs1057147 had a stronger association with lymph node metastasis than the G allele. • The binding mode of miR-3144-5p or miR-3619-3p to MSLN was altered by the mutation of rs1057147.

Association between macrophage migration inhibitory factor-173G/C polymorphism and psoriasis risk: A meta-analysis.

Background The association between macrophage migration inhibitory factor (MIF)-173G/C polymorphism and psoriasis risk has been reported in several studies with inconsistent conclusions. Aims This study aims to obtain a more convincing estimate of the relationship between the MIF-173G/C polymorphism and psoriasis risk. Methods Web of Science, EMBASE, PubMed, Wan Fang Database and Chinese National Knowledge Infrastructure (CNKI) were searched up to September 2021 and eligible studies were collected. The pooled odds ratios with 95% confidence intervals were calculated to estimate the effects of MIF-173G/C polymorphism on psoriasis risk under different genetic models. All analyses were conducted using the STATA12.0 software. Results A total of 1101 psoriasis cases and 1320 healthy controls from 6 relevant studies were included in this meta-analysis. Pooled analysis suggested that MIF-173G/C polymorphism was associated with increased psoriasis risk under the allelic model (C vs. G: odds ratio = 1.30, 95% confidence interval = 1.04-1.63, P = 0.020), heterozygous model (GC vs. GG: odds ratio = 1.53, 95% confidence interval = 1.05-2.22, P = 0.027) and dominant model (CC + GC vs. GG: odds ratio = 1.51, 95% confidence interval = 1.05-2.18, P = 0.027). Limitation Very few studies on the MIF-173G/C polymorphism in psoriasis have been reported till now, thus the number of studies included in the present meta-analysis was relatively small. Due to the number of studies being relatively small and the lack of raw data, stratified analysis by ethnicity or type of psoriasis was not carried out. Conclusion This meta-analysis demonstrated that MIF-173G/C polymorphism might be related to psoriasis risk. Carriers of the C allele and the GC genotype might have higher odds to present with psoriasis.

Rs719725 Polymorphism and Colorectal Cancer Susceptibility: A Meta-analysis.

Many studies have suggested an association between 9p24 rs719725 polymorphism and colorectal cancer (CRC) risk, but with inconsistent results. This meta-analysis aimed to summarise the overall association of rs719725 polymorphism with CRC risk. Nine eligible articles with 21 case-control studies (16015 CRC patients and 19341 controls) on the rs719725 polymorphism and CRC susceptibility from four electronic databases (Web of Science, PubMed, SinoMed, and EMBASE) were retrieved and analysed. The association was evaluated with publication bias, pooled OR (odds ratio), and corresponding 95% CI (confidence interval). The pooled results indicated a significant association between the increased CRC risk and rs719725 polymorphism in dominant ([OR] 1.220, [95%CI] 1.161-1.282), recessive (1.166, 1.102-1.234), allele (1.142, 1.102-1.184), homozygous (1.306, 1.212-1.406), and heterozygous (1.18, 1.129-1.234) genetic models. The ethnicity-stratified analyses found a consistently significant association. In the stratification analysis with the source of controls, such significant association was also detected amid the population-based studies under the four former genetic models. Taken together, this meta-analysis indicates that rs719725 genetic variants are associated with an increased risk of CRC among Caucasians and population-based studies. Further relevant research is warranted to confirm these findings. Key Words: Colorectal cancer, rs719725, Polymorphism, Meta-analysis, Stratification analysis.

Association of MTR A2756G and MTRR A66G Polymorphisms With Male Infertility: An Updated Meta-Analysis.

The objective of the present study was to find out the association of folate genes MTR A2756G and MTRR A66G polymorphisms with the risk of male infertility. The databases of Google Scholar, PubMed, and Science Direct were searched to find relevant studies. Data were extracted from the eligible studies and were analyzed for pooled up odds ratio (OR) with 95% confidence interval (CI). Review Manager 5.4 was used for statistical analysis. Nineteen case-control studies were included in this meta-analysis which comprised 3621 cases and 3327 controls. Pooled analysis revealed that there is a significant association between MTR A2756G polymorphism with male infertility except for the dominant model. The ORs and 95% CI for each genetic model were as follows: 1.21 [1.03-1.42] for the allele model (G vs. A), 2.31 [1.38-3.96] for the additive model (GG vs. AA), 1.17 [0.98-1.38] for the dominant model (GG+AG vs. AA) and 2.10 [1.55-2.86] for the recessive model (GG vs. AG+AA). MTRR A66G has no noticeable association with male infertility. The current meta-analysis suggests that MTR A2756G polymorphism might be a potential risk factor for male infertility. In the future, the sample size should be increased to confirm the present results.

Association of insulin signaling pathway-related gene polymorphisms and gene-gene interactions with MAFLD in obese children.

Insulin signaling pathway plays an important role in metabolic associated fatty liver disease (MAFLD), however, the association between polymorphisms of genes related to insulin signaling pathway and MAFLD remains unclear. This study aims to investigate the association between insulin signaling pathway-related gene polymorphisms and gene-gene interactions with MAFLD susceptibility in obese children so as to provide scientific basis for further study of genetic mechanism. A total of 502 obese children with MAFLD who admitted to Hunan Provincial Children's Hospital from September 2019 to October 2021, were recruited as a case group, and 421 obese children with non-MAFLD admitted during the same period were recruited as a control group. Socio-demographic information, preterm birth history, eating habits, and exercise status of the subjects were collected by inquiry survey, and anthropometric information was collected by physical measurement. At the same time, 2 mL of venous blood was collected to extract DNA, and the polymorphism of insulin signaling pathway-related genes (5 representative candidate genes, 12 variants) was detected. Multivariate Logistic regression analysis was used to investigate the association between insulin signaling pathway-related gene polymorphisms and MAFLD in obese children. After adjusting for confounder factors, INS rs3842748 was significantly associated with the risk of MAFLD in obese children in allele, heterozygous, and dominant models [OR and 95% CI 1.749 (1.053 to 2.905), 1.909 (1.115 to 3.267), 1.862 (1.098 to 3.157), all P<0.05]; INS rs3842752 was significantly associated with the risk of MAFLD in obese children in heterozygous and dominant models [OR and 95% CI 1.736 (1.028 to 2.932), 1.700 (1.015 to 2.846), all P<0.05]. NR1H3 rs3758674 was significantly correlated with the risk of MAFLD in obese children in allele model [OR and 95% CI 0.716 (0.514 to 0.997), P<0.05]. SREBP-1c rs2297508 was significantly associated with the risk of MAFLD in obese children in allele and dominant models [OR and 95% CI 0.772 (0.602 to 0.991) and 0.743 (0.557 to 0.991), all P<0.05]. SREBP-1c rs8066560 was significantly associated with the risk of MAFLD in obese children in allele, heterozygous, and dominant models [OR and 95% CI 0.759 (0.589 to 0.980), 0.733 (0.541 to 0.992), 0.727 (0.543 to 0.974), all P<0.05]. NR1H3 rs3758674 mutant C and SREBP-1c rs2297508 mutant G had interaction in the development of MAFLD in obese children [OR and 95% CI 0.407 (0.173 to 0.954), P<0.05]. The INS, NR1H3, and SREBP-1c gene polymorphisms in the insulin signaling pathway are associated with the susceptibility of MAFLD in obese children, but the functions and mechanisms of these genes need to be further studied.

Association of HHEX and SLC30A8 Gene Polymorphisms with Gestational Diabetes Mellitus Susceptibility: A Meta-analysis.

Genetics plays a role in the development of gestational diabetes mellitus (GDM), which poses serious risks to pregnant women and their children. Several studies have demonstrated a link between GDM susceptibility and rs13266634 C/T polymorphism in SLC30A8 gene and rs1111875 C/T and rs5015480 C/T, which are located near the linkage disequilibrium block containing the IDE, HHEX, and KIF11 genes. However, the results are conflicting. Therefore, we aimed to investigate the association between susceptibility to GDM and HHEX and SLC30A8 gene polymorphisms. PubMed, Web of Science, EBSCO, CNKI, Wanfang Data, VIP, and SCOPUS were used to search for research articles. The quality of the selected literature was evaluated using the Newcastle-Ottawa scale. A meta-analysis was performed using Stata 15.1. Allelic, dominant, recessive, homozygote, and heterozygote models were used for the analysis. Nine articles with 15 studies were included. (1) Four studies about HHEX rs1111875 showed that the C allele was associated with the susceptibility to GDM; (2) three studies on HHEX rs5015480 indicated that the C allele in rs5015480 was significantly associated with GDM; (3) eight studies about SLC30A8 rs13266634 showed that the C allele was significantly associated with the susceptibility to GDM; and (4) a subgroup analysis showed that the rs5015480 polymorphism in HHEX and rs13266634 polymorphism in SLC30A8 gene were associated with GDM susceptibility in Asians. The meta-analysis provided evidence that the C allele in rs1111875 and rs5015480 in HHEX and rs13266634 in SLC30A8 can increase the risk of GDM.PROSPERO registration number CRD42022342280.

Association between Vitamin D receptor (VDR) gene polymorphisms and hypertensive disorders of pregnancy: a systematic review and meta-analysis.

Hypertensive disorders of pregnancy (HDP) are currently one of the major causes of pregnancy-related maternal and fetal morbidity and mortality worldwide. Recent studies provide evidence that maternal Vitamin D receptor (VDR) gene polymorphisms probably play a key role by affecting the biological function of vitamin D in some adverse pregnancy outcomes, while the relationship between the VDR gene polymorphisms and the risk of HDP remains controversial in current studies. This systematic review and meta-analysis aimed to comprehensively evaluate the association of the VDR gene polymorphisms with HDP susceptibility. This meta-analysis follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and a protocol has been registered in the PROSPERO (ID: CRD42022344383) before commencing this review. PubMed, Web of Science, Embase, and the Cochrane Library databases were searched until January 21, 2023. Case-control and cohort studies that reported the association of the VDR gene polymorphisms with HDP were included. The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS) for non-randomized studies. The odds ratios (ORs) with corresponding 95% confidence intervals (CIs) of the five models (allele model, dominant model, recessive model, homozygous model, heterozygous model) were pooled respectively, and subgroup analysis was performed based on ethnicity. A total of ten studies were included. The VDR gene ApaI polymorphism was associated with HDP susceptibility in the dominant model (OR: 1.38; 95% CI [1.07-1.79]; P=0.014) and the heterozygote model (OR: 1.48; 95% CI [1.12-1.95]; P=0.006). In subgroup analysis, the heterozygote model (OR: 2.06; 95% CI [1.21-3.52]; P=0.008) of the ApaI polymorphism was associated with HDP in Asians, but not in Caucasians. The VDR gene ApaI polymorphism may be associated with HDP susceptibility. Insufficient evidence to support the existence of ethnic differences in this association.

Enlightening the association between TNF-α -308 G > A and migraine: a meta-analysis with meta-regression and trial sequential analysis

BackgroundMigraine is a complex neurological disorder that is characterized by a "lower threshold of neuronal hyperexcitability" with distinctive periodicity and complex vascular dysfunction. Genetic factors have impacted incredibly on the susceptibility of migraine and one such example is the TNF-α 308G > A.AimTherefore, we aim to provide a glimpse of the association of the TNF-α 308G > A risk on the susceptibility of migraine.MethodThe pooled odds ratio with the associated 95% of confidence interval were calculated using different genetic models. Heterogeneity was accessed by using Cochran's Q Test and I2 statistics and Begg's and Egger's tests were used for finding the publication bias, tests were two-sided, and a p-value of < 0.05 was considered statistically significant. The Trial Sequential Analysis with Meta-regression Analysis were also utilized to find out the sample size requirement for meta-analysis to avoid type I error and source of heterogeneity respectively.ResultA total of 13 studies with cases: 7193 and controls: 23,091 were included and after using different genetic models, no overall association with migraine and its clinical subtype migraine with aura was observed (Allele model “OR: 1.28, 95% C.I. [0.96–1.69] and OR: 0.99,95% C.I. [0.69–1.42]) respectively. Interestingly, after sub-grouping using the “ethnicity criteria” in the migraine group, it was observed that the allelic genetic model and the dominant model were found to be significantly associated with the Asian ethnic group (OR: 1.79, 95% C.I. [1.13–2.84], and OR: 1.85, 95% C.I. [1.0927; 3.1580].ConclusionIn conclusion, the present meta-analysis has provided evidence that 308G > A increases the risk of migraine only in the Asian population.

INSR and ISR‑1 gene polymorphisms and the susceptibility of essential hypertension: A meta‑analysis.

INSR and ISR-1 may be candidate genes for essential hypertension (EH). However, the genetic association between the INSR and ISR-1 gene polymorphisms and EH risk remains contradictory. To determine a more precise association of the INSR and ISR-1 gene polymorphisms and EH, the present study performed a meta-analysis. Eligible studies up to Jan 2021 were retrieved from multiple databases including PubMed, Embase, Web of Science and China National Knowledge Infrastructure. The pooled odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the genetic associations between the allele, dominant and recessive models of INSR Nsil, RsaI and ISR-1 G972R polymorphisms and EH susceptibility. A total of 10 case-control studies encompassing 2,782 subjects including 1,289 cases and 1,493 controls were evaluated for the present meta-analysis. Neither of the allele, dominant and recessive models of INSR Nsil and ISR-1 G972R polymorphisms was associated with EH risk (P>0.05). While the allele [P=0.0008, OR=0.58, (95% CI)=(0.42, 0.80)], dominant [P=0.02, OR=0.59, (95% CI)=(0.38, 0.92)] and recessive models [P=0.003, OR=0.38, (95% CI)=(0.20, 0.72)] of INSR Rsal polymorphism were associated with decreased risk of EH. Subgroup analysis according to ethnicity showed that the significant associations between the allele, dominant and recessive models of INSR Rsal polymorphism and EH risk were observed in Caucasian populations, but not in Asian populations (P>0.05). In conclusion, the INSR Rsal polymorphism is probably a protective factor for EH. To identify the result, additional case-control designed research with larger numbers of subjects are required.

ZNF804A intronic variant rs1344706 and NGRN rs12807809 genetic polymorphisms and risk of schizophrenia in Bangladesh

BackgroundGenetic polymorphism exerts an undeniable impact on schizophrenia (SCZ) pathogenesis. Two polymorphisms, including rs1344806 of ZNF804A and rs12807809 of NRGN gene have been identified as susceptible candidates bearing the risk of SCZ. The target of this experimental study is to investigate the role of these polymorphisms with SCZ in native Bangladeshi people. MethodsFor this study, 220 schizophrenic patients and 204 non-schizophrenic controls were recruited to perform this investigation. For genotyping, tetra-primer ARMS-PCR technique was applied. The Agarose gel electrophoresis system visualized the final genomic products of the desired size. ResultsFrom the genotypic analysis of ZNF804A rs1344706 polymorphism, it was revealed that the minor allele frequency was noticeably increased in the patients than in the healthy population (42.27% vs. 29.17%). Five genetic models showed significantly increased risk of SCZ, including codominant model 1 (1.56-times), codominant model 2 (3.02-times), dominant model (1.86-times), recessive model (2.43-times), and allele model (1.78-times) (p < 0.05). The over-dominant model also had 1.18 times higher risk for SCZ, although the result could not meet the significance level (p > 0.05). Genotyping of rs12807809 unveiled the presence of a comparatively higher genotypic frequency of the minor allele among the patients than in controls (39.09% vs. 17.65%). Every genetic model under investigation showed significantly increased risk for SCZ– codominant model 1 (2.85-times), codominant model 2 (6.45-times), dominant model (3.44-times), recessive model (4.31-times), over-dominant model (2.10-times), and allele model (3.00-times) (p < 0.05). ConclusionThis experimental study concluded that rs1344806 of ZNF804A and rs12807809 of NRGN SNPs are significantly associated with SCZ in the Bangladeshi population.

Evidence of Association between CTLA-4 Gene Polymorphisms and Colorectal Cancers in Saudi Patients.

Cytotoxic T lymphocyte antigen-4 (CTLA-4) has been identified as an immunosuppressive molecule involved in the negative regulation of T cells. It is highly expressed in several types of autoimmune diseases and cancers including colorectal cancer (CRC). (1) Objective: To explore the association between CTLA-4 single nucleotide polymorphisms (SNP) and risk to (CRC) in the Saudi population. (2) Methods: In this case-control study, 100 patients with CRC and 100 matched healthy controls were genotyped for three CTLA-4 SNPs: rs11571317 (-658C > T), rs231775 (+49A > G) and rs3087243 (CT60 G > A), using TaqMan assay method. Associations were evaluated using odds ratios (ORs) and 95% confidence intervals (95% CIs) for five inheritance models (co-dominant, dominant, recessive, over-dominant and log-additive). Furthermore, CTLA-4 expression levels were evaluated using quantitative real-time PCR (Q-RT-PCR) in colon cancer and adjacent colon tissues. (3) Results: Our result showed a significant association of the G allele (OR = 2.337, p < 0.0001) and GG genotype of the missense SNP +49A > G with increased risk of developing CRC in codominant (OR = 8.93, p < 0.0001) and recessive (OR = 16.32, p < 0.0001) models. Inversely, the AG genotype was significantly associated with decreased risk to CRC in the codominant model (OR = 0.23, p < 0.0001). In addition, the CT60 G > A polymorphism exhibited a strong association with a high risk of developing CRC for the AA genotype in codominant (OR = 3.323, p = 0.0053) and in allele models (OR = 1.816, p = 0.005). No significant association was found between -658C > T and CRC. The haplotype analysis showed that the G-A-G haplotype of the rs11571317, rs231775 and rs3087243 was associated with high risk for CRC (OR = 57.66; p < 0.001). The CTLA-4 mRNA gene expression was found significantly higher in tumors compared to normal adjacent colon samples (p < 0.001). (4) Conclusions: Our findings support an association between the CTLA-4 rs231775 (+49A > G) and rs3087243 (CT60 G > A) polymorphisms and CRC risk in the Saudi population. Further validation in a larger cohort size is needed prior to utilizing these SNPs as a potential screening marker in the Saudi population.

Parent-offspring genotyped trios unravelling genomic regions with gametic and genotypic epistatic transmission bias on the cattle genome.

Several biological mechanisms affecting the sperm and ova fertility and viability at developmental stages of the reproductive cycle resulted in observable transmission ratio distortion (i.e., deviation from Mendelian expectations). Gene-by-gene interactions (or epistasis) could also potentially cause specific transmission ratio distortion patterns at different loci as unfavorable allelic combinations are under-represented, exhibiting deviation from Mendelian proportions. Here, we aimed to detect pairs of loci with epistatic transmission ratio distortion using 283,817 parent-offspring genotyped trios (sire-dam-offspring) of Holstein cattle. Allelic and genotypic parameterization for epistatic transmission ratio distortion were developed and implemented to scan the whole genome. Different epistatic transmission ratio distortion patterns were observed. Using genotypic models, 7, 19 and 6 pairs of genomic regions were found with decisive evidence with additive-by-additive, additive-by-dominance/dominance-by-additive and dominance-by-dominance effects, respectively. Using the allelic transmission ratio distortion model, more insight was gained in understanding the penetrance of single-locus distortions, revealing 17 pairs of SNPs. Scanning for the depletion of individuals carrying pairs of homozygous genotypes for unlinked loci, revealed 56 pairs of SNPs with recessive epistatic transmission ratio distortion patterns. The maximum number of expected homozygous offspring, with none of them observed, was 23. Finally, in this study, we identified candidate genomic regions harboring epistatic interactions with potential biological implications in economically important traits, such as reproduction.

Human and pathogen genotype-by-genotype interactions in the light of coevolution theory.

Antagonistic coevolution (i.e., reciprocal adaptation and counter-adaptation) between hosts and pathogens has long been considered an important driver of genetic variation. However, direct evidence for this is still scarce, especially in vertebrates. The wealth of data on genetics of susceptibility to infectious disease in humans provides an important resource for understanding host-pathogen coevolution, but studies of humans are rarely framed in coevolutionary theory. Here, I review data from human host-pathogen systems to critically assess the evidence for a key assumption of models of host-pathogen coevolution-the presence of host genotype-by-pathogen genotype interactions (G×G). I also attempt to infer whether observed G×G fit best with "gene-for-gene" or "matching allele" models of coevolution. I find that there are several examples of G×G in humans (involving, e.g., ABO, HBB, FUT2, SLC11A1, and HLA genes) that fit assumptions of either gene-for-gene or matching allele models. This means that there is potential for coevolution to drive polymorphism also in humans (and presumably other vertebrates), but further studies are required to investigate how widespread this process is.

The Role of Integrin Beta 3 Polymorphisms in Coronary Artery Disease: A Systematic Review and Meta-analysis

Objectives: The literature on the role of integrin beta 3 (ITGB3) exonic variants in coronary artery disease (CAD) and lipid outcomes is scarce. However, the findings remained uncertain and still not clear. Therefore, the current study aims to determine the association of rs5918 polymorphism with coronary artery disease. Methodology: All the eligible literature published in the English language from February 3, 2005, up to December 19, 2021, were searched by using different electronic databases and extracted all the required information from the available literature. The statistical analysis was performed through the MetaGenyo program, and pooled odds ratios (ORs) were calculated to determine the association between rs5918 and CAD. Results: The final analysis includes four studies, and the overall rs5918 risk allele in all the tested genetic models as follow: allelic model: OR 0.80 CI 0.41-1.58; homozygote model: OR 1.66, 95% CI 0.20-2.16; recessive model: OR 0.71 CI 0.44-1.14; dominant model: OR 0.81 CI 0.22-3.03. In addition, the lipid outcomes, including lipoproteins, cholesterol, and triglycerides were associated with increased disease risk. The shapes of the funnel plots suggest no publication bias in our study. Conclusion: In conclusion, our final pooled analysis revealed a non-significant role of this exonic polymorphism in coronary artery disease that may exert its effect by modulating various lipid parameters. However, more studies are required with a larger cohort size that may give us conclusive results in the future.

The Role of Genetic Variants in the Long Non-Coding RNA Genes MALAT1 and H19 in the Pathogenesis of Childhood Obesity.

Long non-coding RNAs (lncRNAs) play important roles in the maintenance of metabolic homeostasis. Recently, many studies have suggested that lncRNAs, such as Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1) and Imprinted Maternally Expressed Transcript (H19), might participate in the pathogenesis of metabolic disorders such as obesity. We conducted a case-control study with 150 Russian children and adolescents aged between 5 and 17 years old in order to assess the statistical association between the single nucleotide polymorphisms (SNPs) rs3200401 in MALAT1 and rs217727 in H19, and the risk of developing obesity in this population. We further explored the possible association of rs3200401 and rs217727 with BMI Z-score and insulin resistance. The MALAT1 rs3200401 and H19 rs217727 SNPs were genotyped using Taqman SNP genotyping assay. The MALAT1 rs3200401 SNP was identified as a risk factor for childhood obesity (p < 0.05) under the dominant and allelic models, and the CT heterozygous genotype was associated with the risk of increased BMI and with insulin resistance. The H19 rs217727 SNP had no significant association with obesity risk (all p > 0.05). Our findings thus suggest that MALAT1 SNP rs3200401 is a potential indicator of obesity susceptibility and pathogenesis in children and adolescents.

Evaluation of the Association between FGFR2 Gene Polymorphisms and Breast Cancer Risk in the Bangladeshi Population.

Breast cancer is considered the most frequent cause of mortality from malignancy among females. Fibroblast growth factor receptor 2 (FGFR2) gene polymorphisms are highly related to the risk of breast cancer. However, no investigation has been carried out to determine the association of FGFR2 gene polymorphisms in the Bangladeshi population. Based on polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), this study was performed to evaluate the association of FGFR2 (rs1219648, rs2420946, and rs2981582) variants in 446 Bangladeshi women (226 cases and 220 controls). A significant association of the FGFR2 rs1219648 variant with breast malignancy was reported in additive model 1 (aOR = 2.87, p < 0.0001), additive model 2 (aOR = 5.62, p < 0.0001), the dominant model (aOR = 2.87, p < 0.0001), the recessive model (aOR = 4.04, p < 0.0001), and the allelic model (OR = 2.16, p < 0.0001). This investigation also explored the significant association of the rs2981582 variant with the risk of breast cancer in additive model 2 (aOR = 2. 60, p = 0.010), the recessive model (aOR = 2.47, p = 0.006), and the allelic model (OR = 1.39, p = 0.016). However, the FGFR2 rs2420946 polymorphism showed no association with breast cancer except in the overdominant model (aOR = 0.62, p = 0.048). Furthermore, GTT (p < 0.0001) haplotypes showed a correlation with breast cancer risk, and all variants showed strong linkage disequilibrium. Moreover, in silico gene expression analysis showed that the FGFR2 level was upregulated in BC tissues compared to healthy tissues. This study confirms the association of FGFR2 polymorphisms with breast cancer risk.

Genetic variants of the vitamin D receptor are related to dynapenia in postmenopausal women

BackgroundDynapenia increases with age and in the case of women is possibly influenced by menopause, yet whether vitamin D affects this increase remains controversial. The influence of genetic variants (single nucleotide polymorphisms) of the vitamin D receptor on dynapenia is an understudied area. AimTo analyze the association between genetic variants of the vitamin D receptor gene and dynapenia in a cohort of community-dwelling postmenopausal women. MethodsWe performed a cross-sectional study of 463 women in a university hospital. Grip strength was used as an indicator of dynapenia. Differences in grip strength among single nucleotide polymorphisms rs11568820 and rs2228570 genotypes of the vitamin D receptor gene were assessed after adjusting for confounding variables, and the percentage of phenotypic variance was estimated by linear regression. ResultsDynapenia (grip strength <20 kg) was diagnosed in 178 of the women (38.45 %). A difference in grip strength, corresponding to variants of the vitamin D receptor gene single nucleotide polymorphism rs11568820, was found when using an additive model of inheritance, with lower grip strength for the TT genotype (ANOVA, p = 0.030, close to the 0.025 significance level determined by Bonferroni correction). Assuming a recessive inheritance model for allele T, the between-group difference in grip strength was significant (TT = 19.79 ± 3.10 kg vs. CC/CT = 21.58 ± 3.49 kg, p = 0.008) after adjusting for age, body mass index, comorbidities, and sociodemographic variables. More women with dynapenia had the TT genotype (60.71 %) than the CC or CT genotype (37.01 %) (p = 0.012). ConclusionThis study demonstrates that the TT genotype of the rs11568820 SNP of the vitamin D receptor gene was associated with decreased grip strength in community-dwelling postmenopausal women.

Correlation of Q223R and K109R polymorphisms in leptin receptor gene with susceptibility of breast cancer: A systematic review and meta-analysis.

Increasing evidence has suggested a strong association of Q223R (rs1137101) and K109R (rs1137100) polymorphisms in leptin receptor (LEPR) gene with susceptibility of breast cancer (BC), but inconsistent results were obtained. To provide a quantitative assessment of this association, a systematic review and meta-analysis was performed. A literature search of PubMed, EMBASE, Google Scholar, and the Chinese National Knowledge Infrastructure was collected. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. A total of 20 case-control studies for Q223R polymorphism and 8 case-control studies for K109R polymorphism were included. Significant association between Q223R polymorphism and BC risk was not found in total, Asian or Caucasian population, but in African population: allelic model, OR = 0.72, 95% CI = 0.60-0.86, p < 0.001; recessive model, OR = 0.67, 95%CI = 0.52-0.87, P = 0.003; dominant model, OR = 1.58, 95% CI = 1.15-2.17, p = 0.004; homozygous model, OR = 0.51, 95% CI = 0.36-0.78, p < 0.001. Significant association between K109R polymorphism and BC risk was not found in total or Caucasian population, but in Asian population: dominant model, OR = 0.24, 95% CI = 0.07-0.84, p = 0.03; heterozygous model, OR = 1.87, 95% CI = 1.07-3.26, p = 0.03. The available evidence suggests that Q223R polymorphism may be significantly associated with BC risk in African population. K109R polymorphism may be significantly associated with BC risk in Asian population.