Acute Appendicitis (AA) is an inflammatory condition of the vermiform appendix in the caecum of the colon. Genetic polymorphisms have been suggested as risk factors predisposing to AA susceptibility but have remained relatively unknown, due to insufficient sample size in previous analyses. Therefore, the primary research aim was to identify genetic variants associated with AA. It was hypothesised that gene polymorphisms associated with AA will provide a connection to other diet-related inflammatory diseases. Genetic variants associated with AA were studied via a Genome-Wide Association Scan (GWAS) using the Global Biobank Meta-Analysis Initiative (GBMI). The GBMI is a collaborative consortium of 23 biobanks with a publicly released repository of de-identified genetic data linked with digital health records spanning 4 continents with a study population size of over 2.2 million consented individuals of multiple ancestral backgrounds1. A linear regression model was used to estimate the association between single nucleotide polymorphisms (SNPs), across the human genome, and AA by each contributing biobank. The results were then meta-analysed with a total of 32,706 cases and 1,075,763 controls. In the present study, the free open-source Complex Traits Genetic Virtual Lab (CTG-VL) platform was used to access, analyse, and visualise the GWAS summary statistics of AA2. Genome-wide significantly associated SNPs (p-value < 5 x 10-8) were further searched for their associations with health-related traits in publicly available GWAS summary statistics. Upon analysis, significantly associated SNPs for AA were identified within or nearby nine genes. HLX, NKX2-3, LTBR, and DLEU1 are genes involved in immune responses; IRF8 associated with maturation of myeloid cells; OSR-1 responsible for transmembrane ion transporter activity; NCALD a regulator of G protein-coupled signal transduction. In addition, based on the hypothesis, the SNP of key clinical importance was the HLA-C rs2524046 (p-value = 2.38 x 10-8), with the AA risk-increasing allele C being also strongly associated with a higher risk of coeliac disease (CD). The CD is an autoimmune condition where gluten, a protein present in grains such as barley, rye, and wheat, elicits an inflammatory response that results in damage to the small intestine lining. Considering how both AA and CD share the same SNP, it is possible to speculate whether gluten initiates a similar pathophysiological mechanism that exacerbates inflammation in the vermiform appendix in AA. In conclusion, the top AA associated SNPs suggests its development could be due to immunological responses influenced by dietary nutrient intake. The HLA-C SNP is common to AA and CD, suggesting that the gluten protein found in certain cereal grains possibly contributes to the pathophysiology of AA like CD. This warrants further investigations into whether dietary gluten could play a key role in AA development.

This review discusses epigenetic mechanisms and the relationship of infertility in men and women in relation to parameters pertaining to nutrition. The prevalence of infertility worldwide is 8–12 %, and one out of every eight couples receives medical treatment. Epigenetic mechanisms, aging, environmental factors, dietary energy and nutrients and non-nutrient compounds; more or less energy intake, and methionine come into play in the occurrence of infertility. It also interacts with vitamins B12, D and B6, biotin, choline, selenium, zinc, folic acid, resveratrol, quercetin and similar factors. To understand the molecular mechanisms regulating the expression of genes that affect infertility, the environment, the role of genotype, age, health, nutrition and changes in the individual's epigenotype must first be considered. This will pave the way for the identification of the unknown causes of infertility. Insufficient or excessive intake of energy and certain macro and micronutrients may contribute to the occurrence of infertility as well. In addition, it is reported that 5–10 % of body weight loss, moderate physical activity and nutritional interventions for improvement in insulin sensitivity contribute to the development of fertility. Processes that pertain to epigenetics carry alterations which are inherited yet not encoded via the DNA sequence. Nutrition is believed to have an impact over the epigenetic mechanisms which are effective in the pathogenesis of several diseases like infertility. Epigenetic mechanisms of individuals with infertility are different from healthy individuals. Infertility is associated with epigenetic mechanisms, nutrients, bioactive components and numerous other factors.

Recent genome-wide association studies (GWAS) on the dietary habits of the Japanese population have shown that an effect rs671 allele was inversely associated with fish consumption, whereas it was directly associated with coffee consumption. Although meat is a major source of protein and fat in the diet, whether genetic factors that influence meat-eating habits in healthy populations are unknown. This study aimed to conduct a GWAS to find genetic variations that affect meat consumption in a Japanese population. We analysed GWAS data using 14 076 participants from the Japan Multi-Institutional Collaborative Cohort (J-MICC) study. We used a semi-quantitative food frequency questionnaire to estimate food intake that was validated previously. Association of the imputed variants with total meat consumption per 1000 kcal energy was performed by linear regression analysis with adjustments for age, sex, and principal component analysis components 1–10. We found that no genetic variant, including rs671, was associated with meat consumption. The previously reported single nucleotide polymorphisms that were associated with meat consumption in samples of European ancestry could not be replicated in our J-MICC data. In conclusion, significant genetic factors that affect meat consumption were not observed in a Japanese population.

Identification of a new axis of angiotensin-converting enzyme 2 (ACE2)/angiotensin (1–7)/Mas receptor, in the renin-angiotensin system (RAS), has opened a new insight regarding the role of RAS and angiotensin in higher brain functions. ACE2 catabolizes angiotensin II and produces angiotensin (1–7), an agonist of Mas receptor. Mice lacking the Mas receptor (angiotensin 1–7 receptor) exhibit anxiety-like behaviours. The present study was conducted to test the hypothesis of the involvement of ACE2 genetic variant (G8790A) on response to selective serotonin reuptake inhibitors (SSRIs). In a randomised control trial, 200 newly diagnosed Iranian patients with major depressive disorder completed 6 weeks of fluoxetine or sertraline treatment. Patients with a reduction of 50% or more in the Hamilton Rating Scale for Depression score were considered responsive to treatment. G8790A polymorphism was determined in extracted DNAs using restriction fragment length polymerase chain reaction method. Our results show that the A allele and AA and GA genotypes were significantly associated with better response to SSRIs (p = 0.008; OR = 3.4; 95% CI = 1.4–8.5 and p = 0.027; OR = 3.3, 95% CI = 1.2–9.2, respectively). Moreover, patients with GA and AA genotypes responded significantly better to sertraline (p = 0.0002; OR = 9.1; 95% CI = 2.4–33.7). The A allele was significantly associated with better response to sertraline (p = 0.0001; OR = 7.6; 95% CI = 2.5–23.3). In conclusion, our results confirm the role of G8790A in response to some SSRIs.

Diets varying in SFA and MUFA content can impact glycaemic control; however, whether underlying differences in genetic make-up can influence blood glucose responses to these dietary fatty acids is unknown. We examined the impact of dietary oils varying in SFA/MUFA content on changes in blood glucose levels (primary outcome) and whether these changes were modified by variants in the stearoyl-CoA desaturase (SCD) gene (secondary outcome). Obese men and women participating in the randomised, crossover, isoenergetic, controlled-feeding Canola Oil Multicenter Intervention Trial II consumed three dietary oils for 6 weeks, with washout periods of ˜6 weeks between each treatment. Diets studied included a high SFA/low MUFA Control oil (36·6 % SFA/28·2 % MUFA), a conventional canola oil (6·2 % SFA/63·1 % MUFA) and a high-oleic acid canola oil (5·8 % SFA/74·7 % MUFA). No differences in fasting blood glucose were observed following the consumption of the dietary oils. However, when stratified by SCD genotypes, significant SNP-by-treatment interactions on blood glucose response were found with additive models for rs1502593 (P = 0·01), rs3071 (P = 0·02) and rs522951 (P = 0·03). The interaction for rs3071 remained significant (P = 0·005) when analysed with a recessive model, where individuals carrying the CC genotype showed an increase (0·14 (sem 0·09) mmol/l) in blood glucose levels with the Control oil diet, but reductions in blood glucose with both MUFA oil diets. Individuals carrying the AA and AC genotypes experienced reductions in blood glucose in response to all three oils. These findings identify a potential new target for personalised nutrition approaches aimed at improving glycaemic control.

Tuberculosis (TB) is a common infectious disease, and the present study aims to explore the associations of single nucleotide polymorphisms (SNPs) at rs1135216 and rs1057141 of transporter-associated antigen processing (TAP1) and rs2228396 of TAP2 with pulmonary tuberculosis (PTB) risk. A case–control study including 168 smear-positive PTB cases and 251 controls was conducted. Genotyping of the SNPs at rs1135216, rs1057141 and rs2228396 was performed, and their associations with PTB risk were analysed with SPSS software version 19.0. After conducting stratification for age, a significant association was detected for rs1057141 with increased PTB risk (OR = 0.17, 95% CI 0.04–0.79) among those aged ≥60 years. For those aged <60 years, a marginally significant association was detected between rs1135216 TC/CC and PTB risk (OR = 1.97, 95% CI 0.93–4.19). Haplotype analysis revealed that the haplotype AT at rs1135216 and rs2228396, as well as AAT at rs1057141, rs1135216 and rs2228396, was associated with increased PTB risk, and the ORs were 2.83 (95% CI 1.30–6.14) and 2.89 (95% CI 1.34–6.27), respectively. Rs1057141 is a genetic predictor of reduced PTB risk for those aged ≥60 years, while rs1135216 might be a potential genetic predictor for those aged <60 years. Haplotype AT at rs1135216 and rs2228396, as well as AAT at rs1057141, rs1135216 and rs2228396, is a genetic marker that may predict PTB risk.

Optimal maternal long-chain PUFA (LCPUFA) status is essential for the developing fetus. The fatty acid desaturase (FADS) genes are involved in the endogenous synthesis of LCPUFA. The minor allele of various FADS SNP have been associated with increased maternal concentrations of the precursors linoleic acid (LA) and α-linolenic acid (ALA), and lower concentrations of arachidonic acid (AA) and DHA. There is limited research on the influence of FADS genotype on cord PUFA status. The current study investigated the influence of maternal and child genetic variation in FADS genotype on cord blood PUFA status in a high fish-eating cohort. Cord blood samples (n 1088) collected from the Seychelles Child Development Study (SCDS) Nutrition Cohort 2 (NC2) were analysed for total serum PUFA. Of those with cord PUFA data available, maternal (n 1062) and child (n 916), FADS1 (rs174537 and rs174561), FADS2 (rs174575), and FADS1-FADS2 (rs3834458) were determined. Regression analysis determined that maternal minor allele homozygosity was associated with lower cord blood concentrations of DHA and the sum of EPA + DHA. Lower cord blood AA concentrations were observed in children who were minor allele homozygous for rs3834458 (β = 0·075; P = 0·037). Children who were minor allele carriers for rs174537, rs174561, rs174575 and rs3834458 had a lower cord blood AA:LA ratio (P < 0·05 for all). Both maternal and child FADS genotype were associated with cord LCPUFA concentrations, and therefore, the influence of FADS genotype was observed despite the high intake of preformed dietary LCPUFA from fish in this population.

Des données nombreuses mais contradictoires existent à l’heure actuelle sur l’implication du récepteur 2A à la sérotonine (5-HT2AR), codé par le gène HTR2A, dans le trouble dépressif majeur unipolaire [1,3]. Dans notre étude, nous combinons des données cliniques et précliniques pour déterminer l’impact d’une diminution de la transmission sérotoninergique dépendante du 5-HT2AR sur le développement et les caractéristiques des épisodes dépressifs caractérisés. Deux polymorphismes du gène HTR2A (His452Tyr et 102C/T), dont certains allèles entraîneraient une baisse de l’activité fonctionnelle du 5-HT2AR [3], ont été étudiés sur une population de 485 patients caucasiens présentant un épisode dépressif majeur (EDM) dans le cadre d’un trouble dépressif majeur unipolaire. D’autre part, une étude préclinique comparant l’effet d’une administration chronique de corticostérone sur l’apparition d’un phénotype de type dépressif [2] chez des souris mutées pour le Htr2a (Htr2a-/-) et des souris sauvages a été réalisée. Chez les patients, le variant TT du polymorphisme His452Tyr, particulièrement peu fréquent, a été détecté chez deux patients souffrant d’un EDM de type mélancolique. D’autre part, l’allèle C du polymorphisme 102C/T est plus fréquemment retrouvé chez les patients déprimés (p = 0,019) que dans la population générale et les génotypes CC et CT sont associés à des EDM plus sévères à l’HAMD-17 (p = 0,008). D’autre part, les tests comportementaux effectués chez les souris Htr2a-/- montrent que ces dernières développent un phénotype de type dépressif plus marqué par rapport aux souris sauvages (p < 0,01) en réponse à l’administration chronique de corticostérone. Cette étude translationnelle suggère qu’une diminution de la transmission sérotoninergique au niveau du 5-HT2AR pourrait favoriser le développement d’un trouble dépressif majeur unipolaire et entraîner une sévérité plus importante des épisodes dépressifs caractérisés.

The dominating hypothesis among numerous hypotheses explaining the pathogenesis of depressive disorders (DD) is the one involving oxidative and nitrosative stress. In this study, we examined the association between single-nucleotide polymorphisms of the genes encoding SOD2 (superoxide dismutase 2), CAT (catalase), GPx4 (glutathione peroxidase 4), NOS1 (nitric oxide synthase 1), NOS2 (nitric oxide synthase 2), and the development of depressive disorders. Our study was carried out on the DNA isolated from peripheral blood collected from 281 depressed patients and 229 controls. Using TaqMan probes, we genotyped the following six polymorphisms: c.47T > C (p.Val16Ala) (rs4880) in SOD2, c.-89A > T (rs7943316) in CAT, c.660T > C (rs713041) in GPx4, c.-420-34221G > A (rs1879417) in NOS1, c.1823C > T (p.Ser608Leu) (rs2297518), and c.-227G > C (rs10459953) in NOS2. We found that the T/T genotype of the c.47T > C polymorphism was linked with an increased risk of depression. Moreover, the T/T genotype and T allele of c.660T > C increased the risk of DD occurrence, while the heterozygote and C allele decreased this risk. On the other hand, we discovered that the A/A genotype of c.-89A > T SNP was associated with a reduced risk of DD, while the A/T genotype increased this risk. We did not find any correlation between the genotypes/alleles of c.-420-34221G > A, c.1823C > T, and c.-227G > C, and the occurrence of DD. In addition, gene-gene and haplotype analyses revealed that combined genotypes and haplotypes were connected with the disease. Moreover, we found that sex influenced the impact of some SNPs on the risk of depression. Concluding, the studied polymorphisms of SOD2, CAT and GPx4 may modulate the risk of depression. These results support the hypothesis that oxidative and nitrosative stresses are involved in the pathogenesis of depressive disorders.

Single nucleotide polymorphisms (SNPs) able to describe population differences can be used for important applications in livestock, including breed assignment of individual animals, authentication of mono-breed products and parentage verification among several other applications. To identify the most discriminating SNPs among thousands of markers in the available commercial SNP chip tools, several methods have been used. Random forest (RF) is a machine learning technique that has been proposed for this purpose. In this study, we used RF to analyse PorcineSNP60 BeadChip array genotyping data obtained from a total of 2737 pigs of 7 Italian pig breeds (3 cosmopolitan-derived breeds: Italian Large White, Italian Duroc and Italian Landrace, and 4 autochthonous breeds: Apulo-Calabrese, Casertana, Cinta Senese and Nero Siciliano) to identify breed informative and reduced SNP panels using the mean decrease in the Gini Index and the Mean Decrease in Accuracy parameters with stability evaluation. Other reduced informative SNP panels were obtained using Delta, Fixation index and principal component analysis statistics, and their performances were compared with those obtained using the RF-defined panels using the RF classification method and its derived Out Of Bag rates and correct prediction proportions. Therefore, the performances of a total of six reduced panels were evaluated. The correct assignment of the animals to its breed was close to 100% for all tested approaches. Porcine chromosome 8 harboured the largest number of selected SNPs across all panels. Many SNPs were included in genomic regions in which previous studies identified signatures of selection or genes (e.g. ESR1, KITL and LCORL) that could contribute to explain, at least in part, phenotypically or economically relevant traits that might differentiate cosmopolitan and autochthonous pig breeds. Random forest used as preselection statistics highlighted informative SNPs that were not the same as those identified by other methods. This might be due to specific features of this machine learning methodology. It will be interesting to explore if the adaptation of RF methods for the identification of selection signature regions could be able to describe population-specific features that are not captured by other approaches.

Sorghum (Sorghum bicolor (L.) Moench) is an important resource to the national economy and it is essential to assess the genetic diversity in existing sorghum germplasm for better conservation, utilization and crop improvement. The aim of this study was to evaluate the level of genetic diversity within and among sorghum germplasms collected from diverse institutes in Nigeria and Mali using Single Nucleotide Polymorphic markers. Genetic diversity among the germplasm was low with an average polymorphism information content value of 0.24. Analysis of Molecular Variation revealed 6% variation among germplasm and 94% within germplasms. Dendrogram revealed three groups of clustering which indicate variations within the germplasms. Private alleles identified in the sorghum accessions from National Center for Genetic Resources and Biotechnology, Ibadan, Nigeria and International Crop Research Institute for the Semi-Arid Tropics, Kano, Nigeria shows their prospect for sorghum improvement and discovery of new agronomic traits. The presence of private alleles and genetic variation within the germplasms indicates that the accessions are valuable resources for future breeding programs.

Mastitis is an inflammatory disease of the mammary gland, which has a significant economic impact and is an animal welfare concern. This work examined the association between single nucleotide polymorphisms (SNPs) and copy number variations (CNVs) with the incidence of clinical mastitis (CM). Using information from 16 half-sib pairs of Holstein-Friesian cows (32 animals in total) we searched for genomic regions that differed between a healthy (no incidence of CM) and a mastitis-prone (multiple incidences of CM) half-sib. Three cows with average sequence depth of coverage below 10 were excluded, which left 13 half-sib pairs available for comparisons. In total, 191 CNV regions were identified, which were deleted in a mastitis-prone cow, but present in its healthy half-sib and overlapped in at least nine half-sib pairs. These regions overlapped with exons of 46 genes, among which APP (BTA1), FOXL2 (BTA1), SSFA2 (BTA2), OTUD3 (BTA2), ADORA2A (BTA17), TXNRD2 (BTA17) and NDUFS6 (BTA20) have been reported to influence CM. Moreover, two duplicated CNV regions present in nine healthy individuals and absent in their mastitis-affected half-sibs overlapped with exons of a cholinergic receptor nicotinic α 10 subunit on BTA15 and a novel gene (ENSBTAG00000008519) on BTA27. One CNV region deleted in nine mastitis-affected sibs overlapped with two neighbouring long non-coding RNA sequences located on BTA12. Single nucleotide polymorphisms with differential genotypes between a healthy and a mastitis-affected sib included 17 polymorphisms with alternate alleles in eight affected and healthy half-sib families. Three of these SNPs were located introns of genes: MET (BTA04), RNF122 (BTA27) and WRN (BTA27). In summary, structural polymorphisms in form of CNVs, putatively play a role in susceptibility to CM. Specifically, sequence deletions have a greater effect on reducing resistance against mastitis, than sequence duplications have on increasing resistance against the disease.

Birth weight is the earliest available growth trait with considerable impacts on lamb survivability and growth performance traits. This study was conducted to perform a genome-wide association study of birth weight in a meat-type sheep. A total of 132 Lori-Bakhtiari sheep were selected based on estimated of breeding values (EBVs) for BW analyses. The selected animals were genotyped using Illumina Ovine SNP50 Bead Chip. After quality control, a total of 41 323 single-nucleotide polymorphisms (SNPs) and 130 sheep were used for subsequent analyses. Plink 1.90 beta software was used for the analyses. Seven SNPs on chromosomes 1, 16, 19 and 22 were detected based on genome-wide unadjusted P-values (P <10−6), which jointly accounted for 1.2% of total genetic variation. However, based on Bonferroni-adjusted P-values, only three SNPs on chromosome 1 had significant associations with EBVs for birth weight (P <0.05), which jointly explained 0.8% of total genetic variation. A total of seven genes were found in 50 kb intervals from the three significant SNPs on chromosome 1, but only three genes, including RAB6B (a member of RAS oncogene family), Tf serotransferrin and GIGYF2 (a GRB10 interacting GYF protein 2), could be considered as candidate genes for birth weight in future studies. The results of this study may facilitate potential use of the genes involving in growth and production traits for genetic improvement of productivity in sheep.

Taihu pig breeds are the most prolific breeds of swine in the world, and they also have superior economic traits, including high resistance to disease, superior meat quality, high resistance to crude feed and a docile temperament. The formation of these phenotypic characteristics is largely a result of long-term artificial or natural selection. Therefore, exploring selection signatures in the genomes of the Taihu pigs will help us to identify porcine genes related to productivity traits, disease and behaviour. In this study, we used both intra-population (Relative Extend Haplotype Homozygosity Test (REHH)) and inter-population (the Cross-Population Extend Haplotype Homozygosity Test (XPEHH); F-STATISTICS, FST) methods to detect genomic regions that might be under selection process in Taihu pig breeds. As a result, we found 282 (REHH) and 112 (XPEHH) selection signature candidate regions corresponding to 159.78 Mb (6.15%) and 62.29 Mb (2.40%) genomic regions, respectively. Further investigations of the selection candidate regions revealed that many genes under these genomic regions were related to reproductive traits (such as the TLR9 gene), coat colour (such as the KIT gene) and fat metabolism (such as the CPT1A and MAML3 genes). Furthermore, gene enrichment analyses showed that genes under the selection candidate regions were significantly over-represented in pathways related to diseases, such as autoimmune thyroid and asthma diseases. In conclusion, several candidate genes potentially under positive selection were involved in characteristics of Taihu pig. These results will further allow us to better understand the mechanisms of selection in pig breeding.

The study reported in this Research Communication was conducted to investigate the molecular characterisation of buffalo SCAP gene, expression analysis, and the association between single nucleotide polymorphisms and milk production traits in 384 buffaloes. Sequence analysis revealed the SCAP gene had an open reading frame of 3837 bp encoding 1279 amino acids. A ubiquitous expression profile of SCAP gene was detected in various tissues with extreme predominance in the mammary gland during early lactation. Moreover, eleven SNPs in buffalo SCAP gene were identified, six of them (g.1717600A>G, g.1757922C>T, g.1758953G>A, g.1759142C>T, g.1760740G>A, and g.1766036T>C) were found to be significantly associated with 305-day milk yield. Thus, buffalo SCAP could sever as a candidate gene affecting milk production traits in buffalo and the identified SNPs might potentially be genetic markers.