Genome-wide Association Approach Research Articles

New single nucleotide polymorphisms associated with supraventricular arrythmias in patients with pacemaker implantation: genome-wide association approach and pooled DNA strategy

Aims: The objective of this study was to use genome-wide association approach and pooled DNA strategy to search for new genomic loci associated with inter-individual differences in patients with pacemakers placed for sinus node dysfunction in form of sick sinus syndrome (SSS) or tachycardia-bradycardia syndrome (TB) and/or atrio-ventricular (AV) conduction disturbances (AV blocks). Methods and results: Study cohort consisted of 619 patients (recruited from the areas of central Poland) with pacemaker placement and 66 control patients (no pacemaker implantation or history of atrial arrhythmias). We tested association of single nucleotide polymorphisms (SNPs) genotyped using high density microarray platform with 3 groups separated on the basis of the diagnosis associated with pacemaker implantation (AV n=233, SSS n=171, and TB n=215), followed by individual genotyping of most significant SNPs identified in the microarray genomic scan. From the number of 23 initially genotyped SNPs we identified SNP rs2200733 located in the proximity of the PITX2 gene, which showed statistically significant differences between controls (MAF=11%) and 3 pacemaker groups (TB 24.2%; SSS 13.3% and AV 17.4%). The highest statistical significance (p value of 0.005 for minor allele frequency difference in individual genotyping) was observed for SNP in the TB group and AV group (p=0.016) when compared with control. Conclusions: Previous genome-wide association studies implicated a region of human chromosome 4q25 in familial atrial fibrillation (AF) and atrial flutter (AFl), approximately 150 kb distal to the PITX2 homeobox gene, a developmental left-right asymmetry (LRA) gene. In this respect the observed difference in allelic frequency for the investigated PITX2 polymorphism may be associated with the etiology underlying pacemaker placement in the TB group which was, in contrast to SSS group, associated with the frequent episodes of underlying AF. The genome-wide approach might provide an opportunity to identify novel candidate genes and pathways related to the diagnosis of cardiac arrhythmias and indication for the pacemaker implantation. In addition, our findings implicate PITX2 and PITX2-mediated LRA-signaling pathways in prevention of atrial arrhythmias.

Identification of Regions Associated with Variation in Sensitivity to Food-Related Odors in the Human Genome

Humans vary in their ability to smell numerous odors [1-3], including those associated with food [4-6]. Odor sensitivity is heritable [7-11], with examples linking genetic variation for sensitivity to specific odors typically located near olfactory receptor (OR) genes [12-16]. However, with thousands of aromas and few deorphaned ORs [17, 18], there has been little progress toward linking variation at OR loci to odor sensitivity [19, 20]. We hypothesized that OR genes contain the variation that explains much of the differences in sensitivity for odors, paralleling the genetics of taste [21, 22], which affect the flavor experience of foods [23-25]. We employed a genome-wide association approach for ten food-related odors and identified genetic associations to sensitivity for 2-heptanone (p = 5.1 × 10(-8)), isobutyraldehyde (p = 6.4 × 10(-10)), β-damascenone (p = 1.6 × 10(-7)), and β-ionone (p = 1.4 × 10(-31)). Each locus is located in/near distinct clusters of OR genes. These findings increase the number of olfactory sensitivity loci to nine and demonstrate the importance of OR-associated variation in sensory acuity for food-related odors. Analysis of genotype frequencies across human populations implies that variation in sensitivity for these odors is widespread. Furthermore, each participant possessed one of many possible combinations of sensitivities for these odors, supporting the notion that everyone experiences their own unique "flavor world."

Quantitative Assessment of 2q35-rs13387042 Polymorphism and Hormone Receptor Status with Breast Cancer Risk

BackgroundThe association between rs13387042 polymorphism on 2q35 and breast cancer (BC) has been widely evaluated since it was first identified through genome-wide association approach. However, the results have been inconclusive. To investigate this inconsistency, we performed a meta-analysis of all available studies dealing with the relationship between the 2q35-rs13387042 polymorphism and BC.MethodsDatabases including MEDLINE, PubMed, EMBASE, ISI web of science and CNKI (China National Knowledge Infrastructure) were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. The random-effects model was applied, addressing heterogeneity and publication bias.ResultsA total of 24 articles involving 99,772 cases and 164,985 controls were included. In a combined analysis, the summary per-allele odds ratio (OR) for BC of 2q35-rs13387042 polymorphism was 1.13 (95% CI: 1.11–1.16; P<10−5). Significant associations were also detected under co-dominant, dominant and recessive genetic models. In the subgroup analysis by ethnicity, significantly increased risks were found in Asians, Caucasians and Hispanic whites for the polymorphism in all comparisons; whereas no significant associations were found among Africans. In addition, we find 2q35-rs13387042 polymorphism conferred significantly risks for both ER-positive and ER-negative tumors. Furthermore, significant associations were also detected both in PR–positive and PR–negative cancer.ConclusionsOur findings demonstrated that rs13387042-A allele is a risk-conferring factors for the development of BC, especially in Asians, Caucasians and Hispanic whites.

Genome-Wide Association Study of Genetic Predictors of Overall Survival for Non–Small Cell Lung Cancer in Never Smokers

To identify the genetic factors that influence overall survival in never smokers who have non-small cell lung carcinoma (NSCLC), we conducted a consistency meta-analysis study using genome-wide association approaches for overall survival in 327 never smoker patients with NSCLC from The University of Texas MD Anderson Cancer Center (Houston, TX) and 293 cases from the Mayo Clinic (Rochester, MN). We then conducted a two-pronged validation of the top 25 variants that included additional validation in 1,256 patients with NSCLC from Taiwan and assessment of expression quantitative trait loci (eQTL) and differential expression of genes surrounding the top loci in 70 tumors and matched normal tissues. A total of 94 loci were significant for overall survival in both MD Anderson and Mayo studies in the consistency meta-analysis phase, with the top 25 variants reaching a P value of 10(-6). Two variants of these 25 were also significant in the Taiwanese population: rs6901416 [HR, 1.44; 95% confidence interval (CI), 1.01-2.06] and rs10766739 (HR, 1.23; 95%CI, 1.00-1.51). These loci resulted in a reduction of median survival time of at least eight and five months in three populations, respectively. An additional six variants (rs4237904, rs7976914, rs4970833, rs954785, rs485411, and rs10906104) were validated through eQTL analysis that identified significant correlations with expression levels of six genes (LEMD3, TMBIM, ATXN7L2, SHE, ITIH2, and NUDT5, respectively) in normal lung tissue. These genes were also significantly differentially expressed between the tumor and normal lung tissue. These findings identify several novel, candidate prognostic markers for NSCLC in never smokers, with eQTL analysis suggesting a potential biologic mechanism for a subset of these observed associations.

A genome‐wide association study to detect genetic variation for postpartum dysgalactia syndrome in five commercial pig breeding lines

Postpartum dysgalactia syndrome (PDS) in sows is an important disease after parturition with a relevant economic impact, affecting the health and welfare of both sows and piglets. The genetic background of this disease has been discussed and its heritability estimated, but further genetic analyses are lacking in detail. The aim of the current study was to detect loci affecting the susceptibility to PDS through a genome-wide association approach. The study was designed as a family-based association study with matched sampling of affected sows and healthy half- or full-sib control sows on six farms. For the study, 597 sows (322 affected vs. 275 healthy control sows) were genotyped on 62163 single nucleotide polymorphisms (SNPs) using the Illumina PorcineSNP60 BeadChip. After quality control, 585 sows (314 affected vs. 271 healthy control sows) and 49740 SNPs remained for further analysis. Statistics were performed mainly with the r package genabel and included a principal component analysis. A statistically significant genome-wide associated SNP was identified on porcine chromosome (SSC) 17. Further promising results with moderate significance were detected on SSC 13 and on an unplaced scaffold with an older annotation on SSC 15. The PRICKLE2 and NRP2 genes were identified as candidate genes near associated SNPs. Several quantitative trait loci (QTL) have been previously described in these genomic regions, including QTL for mammary gland condition, as teat number and non-functional nipples QTL, as well as QTL for body temperature and gestation length.

A Genome-Wide, Fine-Scale Map of Natural Pigmentation Variation in Drosophila melanogaster

Various approaches can be applied to uncover the genetic basis of natural phenotypic variation, each with their specific strengths and limitations. Here, we use a replicated genome-wide association approach (Pool-GWAS) to fine-scale map genomic regions contributing to natural variation in female abdominal pigmentation in Drosophila melanogaster, a trait that is highly variable in natural populations and highly heritable in the laboratory. We examined abdominal pigmentation phenotypes in approximately 8000 female European D. melanogaster, isolating 1000 individuals with extreme phenotypes. We then used whole-genome Illumina sequencing to identify single nucleotide polymorphisms (SNPs) segregating in our sample, and tested these for associations with pigmentation by contrasting allele frequencies between replicate pools of light and dark individuals. We identify two small regions near the pigmentation genes tan and bric-à-brac 1, both corresponding to known cis-regulatory regions, which contain SNPs showing significant associations with pigmentation variation. While the Pool-GWAS approach suffers some limitations, its cost advantage facilitates replication and it can be applied to any non-model system with an available reference genome.

Genome-wide association study of primary tooth eruption identifies pleiotropic loci associated with height and craniofacial distances.

Twin and family studies indicate that the timing of primary tooth eruption is highly heritable, with estimates typically exceeding 80%. To identify variants involved in primary tooth eruption, we performed a population-based genome-wide association study of ‘age at first tooth’ and ‘number of teeth’ using 5998 and 6609 individuals, respectively, from the Avon Longitudinal Study of Parents and Children (ALSPAC) and 5403 individuals from the 1966 Northern Finland Birth Cohort (NFBC1966). We tested 2 446 724 SNPs imputed in both studies. Analyses were controlled for the effect of gestational age, sex and age of measurement. Results from the two studies were combined using fixed effects inverse variance meta-analysis. We identified a total of 15 independent loci, with 10 loci reaching genome-wide significance (P < 5 × 10−8) for ‘age at first tooth’ and 11 loci for ‘number of teeth’. Together, these associations explain 6.06% of the variation in ‘age of first tooth’ and 4.76% of the variation in ‘number of teeth’. The identified loci included eight previously unidentified loci, some containing genes known to play a role in tooth and other developmental pathways, including an SNP in the protein-coding region of BMP4 (rs17563, P = 9.080 × 10−17). Three of these loci, containing the genes HMGA2, AJUBA and ADK, also showed evidence of association with craniofacial distances, particularly those indexing facial width. Our results suggest that the genome-wide association approach is a powerful strategy for detecting variants involved in tooth eruption, and potentially craniofacial growth and more generally organ development.

Pearls and pitfalls in genetic studies of migraine

Migraine is a prevalent neurovascular brain disorder with a strong genetic component, and different methodological approaches have been implemented to identify the genes involved. This review focuses on pearls and pitfalls of these approaches and genetic findings in migraine. Common forms of migraine (i.e. migraine with and without aura) are thought to have a polygenic make-up, whereas rare familial hemiplegic migraine (FHM) presents with a monogenic pattern of inheritance. Until a few years ago only studies in FHM yielded causal genes, which were identified by a classical linkage analysis approach. Functional analyses of FHM gene mutations in cellular and transgenic animal models suggest abnormal glutamatergic neurotransmission as a possible key disease mechanism. Recently, a number of genes were discovered for the common forms of migraine using a genome-wide association (GWA) approach, which sheds first light on the pathophysiological mechanisms involved. Novel technological strategies such as next-generation sequencing, which can be implemented in future genetic migraine research, may aid the identification of novel FHM genes and promote the search for the missing heritability of common migraine.

Genome-wide association and regional heritability mapping to identify loci underlying variation in nematode resistance and body weight in Scottish Blackface lambs

The genetic architecture underlying nematode resistance and body weight in Blackface lambs was evaluated comparing genome-wide association (GWA) and regional heritability mapping (RHM) approaches. The traits analysed were faecal egg count (FEC) and immunoglobulin A activity against third-stage larvae from Teladorsagia circumcincta, as indicators of nematode resistance, and body weight in a population of 752 Scottish Blackface lambs, genotyped with the 50k single-nucleotide polymorphism (SNP) chip. FEC for both Nematodirus and Strongyles nematodes (excluding Nematodirus), as well as body weight were collected at approximately 16, 20 and 24 weeks of age. In addition, a weighted average animal effect was estimated for both FEC and body weight traits. After quality control, 44 388 SNPs were available for the GWA analysis and 42 841 for the RHM, which utilises only mapped SNPs. The same fixed effects were used in both analyses: sex, year, management group, litter size and age of dam, with day of birth as covariate. Some genomic regions of interest for both nematode resistance and body weight traits were identified, using both GWA and RHM approaches. For both methods, strong evidence for association was found on chromosome 14 for Nematodirus average animal effect, chromosome 6 for Strongyles FEC at 16 weeks and chromosome 6 for body weight at 16 weeks. Across the entire data set, RHM identified more regions reaching the suggestive level than GWA, suggesting that RHM is capable of capturing some of the variation not detected by GWA analyses.

Association of glucokinase regulatory protein polymorphism with type 2 diabetes and fasting plasma glucose: a meta-analysis

Glucokinase regulatory protein (GCKR) which binds to glucokinase (GCK) in the nucleus and inhibits its activity in the presence of fructose-6-phosphate is critical for glucose metabolism. In the past few years, a number of case-control studies have been carried out to investigate the relationship between the GCKR polymorphism and type 2 diabetes (T2D) since it was first identified to be associated with fasting plasma glucose levels, insulin resistance through genome-wide association approach. After that, a number of studies reported that the rs780094 polymorphism in GCKR has been implicated in T2D risk. However, these studies have yielded contradictory results. To investigate this inconsistency, we performed a meta-analysis of 19 studies involving a total of 298,977 subjects for GCKR rs780094 to evaluate its effect on genetic susceptibility for T2D. In a combined analysis, the summary per-allele odds ratio for T2D of the rs780094 polymorphism was 1.11 (95 % CI: 1.07-1.14, P < 10(-5)). Significant results were also observed using dominant (OR = 1.18, 95 % CI: 1.05-1.34, P < 10(-5)) or recessive genetic model (OR = 1.20, 95 % CI: 1.12-1.28, P < 10(-5)). Significant results were found in Asians and Caucasians when stratified by ethnicity. Besides, the polymorphism was found to be significantly associated with increased fasting plasma glucose level. There was strong evidence of heterogeneity, which largely disappeared after stratification by ethnicity. This meta-analysis suggests that the rs780094 polymorphism in GCKR is associated with elevated T2D risk, but these associations vary in different ethnic populations.

Deleted in Colorectal Cancer (DCC) gene polymorphism is associated with H. pylori infection among susceptible Malays from the north-eastern region of Peninsular Malaysia.

Using genome-wide case-control association approach, the current study aimed to determine whether genetic polymorphism(s) is/are associated with H. pylori infection among ethnic Malays from the north-eastern region of Peninsular Malaysia, a region with an exceptionally low prevalence for H. pylori infection and gastric cancer. Twenty-three Malay subjects positive for H. pylori confirmed with urease test and histology were enrolled as "cases" and 37 subjects negative for H. pylori were "controls". Both groups were matched for age and environmental risks. Extracted DNA samples (QIAGEN, Germany) from the venous blood of study subjects were genotyped using the Human Mapping 50k xbal array (Affymetrix, USA). High throughput downstream analyses were then used to determine the significant SNP(s) associated with H. pylori infection. Out of 20,361 SNPs filtered using the genotype association test, the top 1% (203) significant SNPs were selected for functional enrichment analysis. Of the 15 "enriched" SNPs, the rs10502974 which was located within the intronic region of Deleted in Colorectal Cancer (DCC) gene was the SNP most significantly associated with H. pylori infection (p=0.00549). Ethnic Malays is genetically susceptible to H. pylori infection and is possibly mediated through a genetic variation in the DCC gene.

Large-Scale Association Analysis Provides Insights Into the Genetic Architecture and Pathophysiology of Type 2 Diabetes Mellitus

We are amidst an epidemic of cardiometabolic diseases. Despite aggressive lifestyle modifications, the incidence of type 2 diabetes mellitus (T2DM), a potent risk factor for cardiovascular diseases, continues to rise. Simple family histories in patients demonstrate that there is a clustering of the disease in families, and prior studies using genome-wide association (GWA) approaches have identified 56 genetic loci that are associated with T2DM. In a recently published herculean effort, the authors stated that prior GWA study results captured 10% of familial aggregation of the disease. Therefore, to extend understanding of the genetic architecture and molecular basis of T2DM, the authors conducted a meta-analysis (34 840 cases and 114 981 controls) of genetic variants on the Metabochip, a custom array of 196 725 variants designed to facilitate cost-effective follow-up of nominal associations for T2DM, and other metabolic and cardiovascular traits and to enhance fine mapping of established loci. The authors asked whether characterization of increasing numbers of risk loci may provide evidence, at the functional level, that susceptibility to T2DM involves a limited set of molecular processes. The authors conducted a 2-stage meta-analysis: stage-1 meta-analysis consisted of 12 171 T2DM cases and 56 862 controls across 12 GWA studies of individuals of European descent, and the stage-2 meta-analysis consisted of 21 491 T2DM cases and 55 647 controls across 25 studies of individuals of European descent, and 1178 T2DM cases and 2472 controls from 1 study of individuals of Pakistani descent (PROMIS). These participants all underwent genotyping on the Metabochip, in which the T2DM component was comprised of 21 774 variants: 5057 replication single-nucleotide polymorphisms (SNPs) that capture the strongest independent 13 autosomal association signals from the GWA meta-analysis conducted by the Diabetes Genetics Replication and Meta-analysis (DIAGRAM) Consortium, and an additional 16 717 variants chosen from 1000 Genomes Project …

Association between the Melatonin Receptor 1B Gene Polymorphism on the Risk of Type 2 Diabetes, Impaired Glucose Regulation: A Meta-Analysis

BackgroundMelatonin receptor 1B (MTNR1B) belongs to the seven-transmembrane G protein-coupled receptor superfamily involved in insulin secretion, which has attracted considerable attention as a candidate gene for type 2 diabetes (T2D) since it was first identified as a loci associated with fasting plasma glucose level through genome wide association approach. The relationship between MTNR1B and T2D has been reported in various ethnic groups. The aim of this study was to consolidate and summarize published data on the potential of MTNR1B polymorphisms in T2D risk prediction.MethodsPubMed, EMBASE, ISI web of science and the CNKI databases were systematically searched to identify relevant studies. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Heterogeneity and publication bias were also tested.ResultsA total of 23 studies involving 172,963 subjects for two common polymorphisms (rs10830963, rs1387153) on MTNR1B were included. An overall random effects per-allele OR of 1.05 (95% CI: 1.02–1.08; P<10−4) and 1.04 (95% CI: 0.98–1.10; P = 0.20) were found for the two variants respectively. Similar results were also observed using dominant or recessive genetic model. There was strong evidence of heterogeneity, which largely disappeared after stratification by ethnicity. Significant results were found in Caucasians when stratified by ethnicity; while no significant associations were observed in East Asians and South Asians. Besides, we found that the rs10830963 polymorphism is a risk factor associated with increased impaired glucose regulation susceptibility.ConclusionsThis meta-analysis demonstrated that the rs10830963 polymorphism is a risk factor for developing impaired glucose regulation and T2D.

Assessing interactions between the associations of fibroblast growth factor receptor 2 common genetic variants and hormone receptor status with breast cancer risk

Fibroblast growth factor receptor 2 (FGFR2) is a member of a receptor tyrosine kinase gene superfamily, involved in cell growth, invasiveness, motility, and angiogenesis, which has attracted considerable attention as a candidate gene for breast cancer (BC) since it was first identified through genome-wide association approach. In the past few years, the relationship between FGFR2 and BC has been reported in various ethnic groups; however, these studies have yielded contradictory results. To investigate this inconsistency, we performed a meta-analysis of 37 studies involving a total of 288,142 subjects for rs2981582, rs1219648, and rs2420946 polymorphism of the FGFR2 gene to evaluate the effect of FGFR2 on genetic susceptibility for BC. Overall, significantly increased BC risk was associated with these polymorphisms when all studies were pooled into the meta-analysis. In addition, our data indicate that FGFR2 is involved in BC susceptibility and confer its effect primarily in estrogen receptor-positive and progesterone receptor-positive tumors. When stratified by ethnicity, significantly increased risks were found in Caucasian and East Asian populations. However, no significant associations were detected among African descent populations. There was strong evidence of heterogeneity (P < 0.05), which largely disappeared after stratification by ethnicity. This meta-analysis demonstrated that FGFR2 polymorphism is a risk factor associated with increased BC susceptibility, but these associations vary in different ethnic populations.

A genome-wide association analysis of temozolomide response using lymphoblastoid cell lines shows a clinically relevant association with MGMT.

Recently, lymphoblastoid cell lines (LCLs) have emerged as an innovative model system for mapping gene variants that predict the dose response to chemotherapy drugs. In the current study, this strategy was expanded to the in-vitro genome-wide association approach, using 516 LCLs derived from a White cohort to assess the cytotoxic response to temozolomide. Genome-wide association analysis using ∼2.1 million quality-controlled single-nucleotide polymorphisms (SNPs) identified a statistically significant association (P<10(-8)) with SNPs in the O(6)-methylguanine-DNA methyltransferase (MGMT) gene. We also show that the primary SNP in this region is significantly associated with the differential gene expression of MGMT (P<10(-26)) in LCLs and differential methylation in glioblastoma samples from The Cancer Genome Atlas. The previously documented clinical and functional relationships between MGMT and temozolomide response highlight the potential of well-powered genome-wide association studies of the LCL model system to identify meaningful genetic associations.

New single nucleotide polymorphisms associated with differences in platelets reactivity in patients with type 2 diabetes treated with acetylsalicylic acid: genome-wide association approach and pooled DNA strategy

The objective of this study was to use genome-wide association approach and pooled DNA strategy to search for new genomic loci associated with inter-individual differences in platelet reactivity in the diabetic patients during acetylsalicylic acid (ASA) treatment. Study cohort consisted of 297 diabetic patients who had been taking ASA (75mg daily) for at least 3months. We tested association of single nucleotide polymorphisms (SNPs) genotyped using high density microarray platform with several platelet reactivity assays, followed by individual genotyping of most significant SNPs identified in the microarray genomic scan. The highest statistical significance (p value of 0.0001-0.008 in individual genotyping) was observed for SNP located within the regulatory G-protein signaling (RGS) 7 gene (rs2502448) using recessive genetic model. The diabetic patients on ASA treatment and homozygotes for its minor allele were characterized by increased odds ratio of at 3.45 (confidence interval: 1.82-6.53) for high on ASA platelet reactivity (i.e. impaired ASA response) when compared with homozygotes for wild-type allele. The genome-wide approach might provide an opportunity to identify novel candidate genes and pathways related to platelet activation in diabetic patients.

Single Nucleotide Polymorphism and its Application in Mapping Loci Involved in Developing Human Diseases and Traits

Common diseases or traits in humans are often influenced by complex interactions among multiple genes as well as environmental and lifestyle factors rather than being attributable to a genetic variation within a single gene. Identification of genes that confer disease susceptibility can be facilitated by studying DNA markers such as single nucleotide polymorphism (SNP) associated with a disease trait. Genome-wide association approaches offers a systematic analysis of the association of hundreds of thousands of SNPs with a quantitative complex trait. This method has been successfully applied to a wide variety of common human diseases and traits, and has generated valuable findings that have improved the understanding of the genetic basis of many complex traits. This article outlines the general mapping process and methods, highlights the success stories, and describes some limitations and challenges that lie ahead.

Association mapping for soilborne pathogen resistance in synthetic hexaploid wheat

Soilborne pathogens such as cereal cyst nematode (CCN; Heterodera avenae) and root lesion nematode (Pratylenchus neglectus; PN) cause substantial yield losses in the major cereal-growing regions of the world. Incorporating resistance into wheat cultivars and breeding lines is considered the most cost-effective control measure for reducing nematode populations. To identify loci with molecular markers linked to genes conferring resistance to these pathogens, we employed a genome-wide association approach in which 332 synthetic hexaploid wheat lines previously screened for resistance to CCN and PN were genotyped with 660 Diversity Arrays Technology (DArT) markers. Two sequence-tagged site markers reportedly linked to genes known to confer resistance to CCN were also included in the analysis. Using the mixed linear model corrected for population structure and familial relatedness (Q+K matrices), we were able to confirm previously reported quantitative trait loci (QTL) for resistance to CCN and PN in bi-parental crosses. In addition, we identified other significant markers located in chromosome regions where no CCN and PN resistance genes have been reported. Seventeen DArT marker loci were found to be significantly associated with CCN and twelve to PN resistance. The novel QTL on chromosomes 1D, 4D, 5B, 5D and 7D for resistance to CCN and 4A, 5B and 7B for resistance to PN are suggested to represent new sources of genes which could be deployed in further wheat improvement against these two important root diseases of wheat.

Comparison of genome-wide association and regional heritability mapping approaches to identify loci underlying faecal egg count variation in Blackface lambs

Comparison of genome-wide association and regional heritability mapping approaches to identify loci underlying faecal egg count variation in Blackface lambs

Better understanding and new insight of genetic risk loci for gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy, and women with GDM are at increased risk for type 2 diabetes mellitus1. Uncomplicated pregnancy is characterized by insulin resistance and enhanced insulin secretion as a compensatory mechanism to maintain normal glucose tolerance (NGT). However, previous studies showed that in women with GDM during pregnancy, the decreased sensitivity of insulin is at a similar level to NGT, but with more pronounced insulin resistance than NGT. These phenomena might contribute to hyperglycemia in addition to defective insulin release2. Furthermore, women with a history of GDM have been considered a high‐risk group for diabetes mellitus. A study reported from Korea showed that Korean women with a history of GDM have a four‐ to fivefold greater risk of developing postpartum diabetes than the general population (Figure 1). The incidence of type 2 diabetes mellitus within 30 years), prepregnant body mass index (>23 kg/m2), family history of type 2 diabetes mellitus, fasting glucose level at the time of GDM diagnosis (>5.8 mmol/L) and early diagnosis of GDM during pregnancy (<26 weeks)3. In contrast, the putative risk factors for type 2 diabetes mellitus in the Korean population include (but are not limited to) old age, urban living, female sex, obesity, smoking, family history of diabetes, impaired liver function, metabolic syndrome, elevated blood pressure and increased triglycerides4. Although all the risk factors have yet to be identified, the aforementioned variables are the key risk factors for diabetes mellitus in Koreans. Most of these risk factors have also been identified as key risk factors in other places including Europe, South America, North America and Africa. As previously mentioned, some of the risk factors, such as family history of diabetes, lipid profile, high blood pressure and obesity, are common risk factors of both type 2 diabetes mellitus and GDM. Thus, one could question whether GDM is another type of diabetes mellitus or a simple identification of existing type 2 diabetes mellitus during pregnancy when physical, metabolic and psychological changes occur dramatically. It was very difficult to answer the question until the advancement of the Genome‐Wide Association Study (GWAS), which enabled the investigation of genetic background. The genome‐wide association (GWA) approach is an emerging methodology that allows us to identify genetic variants with specific loci that predispose individuals to complex traits and/or diseases.