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Key message: QTL mapping combined with genome-wide association studies, revealed a potential candidate gene for resistance to northern leaf blight in the tropical CATETO-related maize line YML226, providing a basis for marker-assisted selection of maize varieties Northern leaf blight (NLB) is a foliar disease that can cause severe yield losses in maize. Identifying and utilizing NLB-resistant genes is the most effective way to prevent and control this disease. In this study, five important inbred lines of maize were used as parental lines to construct a multi-parent population for the identification of NLB-resistant loci. QTL mapping and GWAS analysis revealed that QTL qtl_YML226_1, which had the largest phenotypic variance explanation (PVE) of 9.28%, and SNP 5-49,193,921 were co-located in the CATETO-related line YML226. This locus was associated with the candidate gene Zm00001d014471, which encodes a pentatricopeptide repeat (PPR) protein. In the coding region of Zm00001d014471, YML226 had more specific SNPs than the other parental lines. qRT-PCR showed that the relative expressions of Zm00001d014471 in inoculated and uninoculated leaves of YML226 were significantly higher, indicating that the expression of the candidate gene was correlated with NLB resistance. The analysis showed that the higher expression level in YML226 might be caused by SNP mutations. This study identified NLB resistance candidate loci and genes in the tropical maize inbred line YML226 derived from the CATETO germplasm, thereby providing a theoretical basis for using modern marker-assisted breeding techniques to select genetic resources resistant to NLB. [ABSTRACT FROM AUTHOR]

Schizophrenia, the most common severe mental illness, leads to a serious decrease in higher functions, mainly to a change in cognitive functions and perception of reality. Both genetic and environmental factors are involved in its pathogenesis; however, its genetic component still needs to be studied. The aim of the study was to identify genetic markers of paranoid schizophrenia in Tatars from the Republic of Bashkortostan. Genome-wide genotyping of DNA samples was carried out on the PsychChip biochip, which included 610 000 single nucleotide polymorphic variants (SNPs). The studied sample consisted of 357 patients with paranoid schizophrenia and 383 healthy individuals of Tatar ethnicity. As a result of the study, the association of the SNP rs12376586 of the MAMDC2 gene located in the region 9q21.13 with the development of paranoid schizophrenia in Tatars living in the Republic of Bashkortostan was established for the first time. [ABSTRACT FROM AUTHOR]

Schizophrenia is a highly hereditary disorder. Genetic risk is associated with a large number of alleles, including common alleles with little effect that can be found in genome-wide association studies. The aim of this study was to study genetic risk factors for the development of schizophrenia in a genome-wide association analysis (GWAS) in Russians from the Republic of Bashkortostan. The studied sample consisted of 320 patients with paranoid schizophrenia and 402 healthy individuals. GWAS genotyping of DNA samples was carried out on the PsychChip biochip, which included 610 000 single nucleotide polymorphic variants (SNPs). [ABSTRACT FROM AUTHOR]

The key to food security is increasing rice yield. Therefore, we performed a genome-wide association study (GWAS) to analyse and identify the effects of plant height (PH), effective tiller number (ETN), heading date (HD) and grain weight per plant (GWPP) on rice yield using 1,220,522 single-nucleotide polymorphisms (SNPs) from 168 rice accessions. The PH, ETN, HD, and GWPP phenotypes of the 168 rice accessions were analysed in 2019, 2020 and 2021, and an abundance of phenotypic variation was found. One QTL for PH was detected on chromosome 4, one QTL for ETN on chromosome 11, two QTLs for GWPP on chromosome 2, and one QTL for HD on chromosome 5, all of which were detected in 3 years of the study period through a general linear model (GLM) and mixed linear model (MLM). We detected two QTLs related to the traits by using multi-trait GWAS. In addition, we identified four novel genes responsible for rice yield. Haplotype analysis indicated that LOC_Os02g07680 was highly associated with GWPP, LOC_Os11g18570 was highly associated with ETN, LOC_Os04g49210 was highly associated with HD, and LOC_Os05g34600 was highly associated with PH. The results provide important genetic information for PH, ETN, HD and GWPP studies, laying the foundation for increasing rice yield. [ABSTRACT FROM AUTHOR]

Over fifteen years, genome-wide association studies (GWAS) have identified several million polymorphic risk markers for schizophrenia, significantly advancing our understanding of the genetic architecture of schizophrenia. The aim of this study was to study genetic risk factors for the development of schizophrenia in a genome-wide association analysis in Russians, Tatars, and Bashkirs from the Republic of Bashkortostan. The studied sample consisted of 816 patients with paranoid schizophrenia and 989 healthy individuals. GWAS genotyping of DNA samples was carried out on the PsychChip, which included 610 000 single nucleotide polymorphic variants (SNPs). As a result of the study, for the first time, an association of SNPs rs73254185 (4p15.2) and rs587778384 of the GNAS gene (20q13.31) with the risk of paranoid schizophrenia in individuals of different ethnicity, Russians, Tatars, and Bashkirs living in the Republic of Bashkortostan, was established, which probably may indicate involvement of the PI4K2B and GNAS genes localized in these chromosomal regions in the pathogenesis of schizophrenia. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: There is increasing evidence for the existence of shared genetic predictors of metabolic traits and neurodegenerative disease. We previously observed a U-shaped association between fasting insulin in middle-aged women and dementia up to 34 years later. In the present study, we performed genome-wide association (GWA) analyses for fasting serum insulin in European children with a focus on variants associated with the tails of the insulin distribution. Methods: Genotyping was successful in 2825 children aged 2–14 years at the time of insulin measurement. Because insulin levels vary during childhood, GWA analyses were based on age- and sex-specific z scores. Five percentile ranks of z-insulin were selected and modelled using logistic regression, i.e. the 15th, 25th, 50th, 75th and 85th percentile ranks (P15–P85). Additive genetic models were adjusted for age, sex, BMI, survey year, survey country and principal components derived from genetic data to account for ethnic heterogeneity. Quantile regression was used to determine whether associations with variants identified by GWA analyses differed across quantiles of log-insulin. Results: A variant in the SLC28A1 gene (rs2122859) was associated with the 85th percentile rank of the insulin z score (P85, p value=3×10−8). Two variants associated with low z-insulin (P15, p value <5×10−6) were located on the RBFOX1 and SH3RF3 genes. These genes have previously been associated with both metabolic traits and dementia phenotypes. While variants associated with P50 showed stable associations across the insulin spectrum, we found that associations with variants identified through GWA analyses of P15 and P85 varied across quantiles of log-insulin. Conclusions/interpretation: The above results support the notion of a shared genetic architecture for dementia and metabolic traits. Our approach identified genetic variants that were associated with the tails of the insulin spectrum only. Because traditional heritability estimates assume that genetic effects are constant throughout the phenotype distribution, the new findings may have implications for understanding the discrepancy in heritability estimates from GWA and family studies and for the study of U-shaped biomarker–disease associations. [ABSTRACT FROM AUTHOR]

Year 2022 marks 25 years since the first mutation in familial autosomal dominant Parkinson's disease was identified. Over the years, our understanding of the role of genetic factors in the pathogenesis of familial and idiopathic forms of Parkinson's disease has expanded significantly – a number of genes for the familial form of the disease have been identified, and DNA markers for an increased risk of developing its sporadic form have been found. But, despite all the success achieved, we are far from an accurate assessment of the contribution of genetic and, even more so, epigenetic factors to the disease development. The review summarizes the information accumulated to date on the genetic architecture of Parkinson's disease and formulates issues that need to be addressed, which are primarily related to the assessment of epigenetic factors in the disease pathogenesis. [ABSTRACT FROM AUTHOR]

As one of the three staple crops, nutritional traits in maize are important for human and animal nutrition. Grain quality-related traits are closely related to grain commercial value. Understanding the genetic basis of quality-related traits in maize would be helpful for breeding high-quality maize varieties. In this study, two association panels (AM122 and AM180) were subjected to genome-wide association analysis of grain quality-related traits, including protein content, oil content, starch content, and fiber content. In total, 98 SNPs (P < 1 × 10−4) were identified to be significantly associated with these four grain quality-related traits. By integrating two sets of public transcriptome data, 31 genes located in 200 kb regions flanking the associated SNP showed high expression during kernel development and were differentially expressed in two maize inbred lines, KA225 and KB035, with significantly different quality. These genes might regulate maize grain quality by participating in plant hormone processes, autophagy processes, and others. All these results could provide important reference information for breeding high‑quality maize varieties. [ABSTRACT FROM AUTHOR]

Forage sorghum (Sorghum bicolor (L.) Moench) is a C4 cereal crop with excellent quality, which is widely cultivated in many countries and regions. Acid detergent fiber is widely found in the stem and leaf tissues of plant, which is the main substance affecting the digestibility of livestock. It has a very important impact on the milk yield and quality of cows, dairy sheep and pigs. In order to further understand its genetic mechanism, we re-sequenced 206 forage sorghum germplasms from different regions of the world and identified 14,570,430 SNPs and 1,967,033 indels. Based on SNP markers, we analyzed the population genetic structure and identified the gene loci related to acid detergent fiber content by genome-wide association analysis (GWAS). Genetic relationship between materials showed that Asian and American sorghum varieties, breeding lines and improved varieties were more diverse, while European varieties were relatively more closely related. These findings provide new clues and directions for further study. GWAS revealed that 8 QTLs harboring 91 genes were found to be associated with acid detergent fiber content. These genes were significantly enriched into 6 major genes involved in cell membrane material transport or enzymes, showing a regional distribution. The findings provide a basis for us to understand the origin and spread of haplotypes related to acid detergent fiber content. The findings will accelerate the study of genetic gain of acid detergent fiber content and help breeders to improve feed quality and stress tolerance of forage sorghum. [ABSTRACT FROM AUTHOR]

Key message: This study identified candidate genes related to fruit yield for an emerging medicinal crop, weeping forsythia. Background: The genetic basis of crop yield is an agricultural research hotspot. Identifying the genes related to yield traits is the key to increase the yield. Weeping forsythia is an emerging medicinal crop that currently lacks excellent varieties. The genes related to fruit yield in weeping forsythia have not been identified. Objective: Thus, we aimed to screen the candidate genes related to fruit yield of weeping forsythia by using genome-wide association analysis. Methods: Here, 60 samples from the same field and source of weeping forsythia were collected to identify its yield-related candidate genes. Association analysis was performed on the variant loci and the traits related to yield, i.e., fruit length, width, thickness, and weight. Results: Results from admixture, neighbor-joining, and kinship matrix analyses supported the non-significant genetic differentiation of these samples. Significant association was found between 2 variant loci and fruit length, 8 loci and fruit width, 24 loci and fruit thickness, and 13 loci and fruit weight. Further search on the 20 kb up/downstream of these variant loci revealed 1 gene related to fruit length, 16 genes related to fruit width, 12 genes related to fruit thickness, and 13 genes related to fruit weight. Among which, 4 genes, namely, WRKY transcription factor 35, salicylic acid-binding protein, auxin response factor 6, and alpha-mannosidase were highly related to the fruit development of weeping forsythia. Conclusion: This study identify four candidate genes related to fruit development, which will provide useful information for the subsequent molecular-assisted and genetic breeding of weeping forsythia. [ABSTRACT FROM AUTHOR]

Background: Litter size is the most important reproductive trait which plays a crucial role in goat production. Therefore, improvement of litter size trait has been of increasing interest in goat industry as small improvement in litter size may lead to large profit. The recent Cashmere goat breeding program produced a high-reproductive genetic line of Arbas Cashmere goat. But the genetic mechanism of high reproduction rate remains largely unknown in this Chinese native goat breed. To address this question, we performed a genome-wide association studies (GWAS) using two groups of goats varying in fecundity. Objectives: Our study was aimed to investigate the significant SNPs and genes associated with high reproduction trait in Inner Mongolia Arbas Cashmere Goat. Methods: We used logistic model association to perform GWAS using 47 goats from high fecundity group (~ 190%) and 314 goats from low fecundity group (~ 130%) of the Arbas Cashmere goat breed. Results: We identified 66 genomic regions associated with genome wide significant level wherein six loci were found to be associated with reproduction traits. Further analysis showed that five key candidate genes including KISS1, KHDRBS2, WNT10B, SETDB2 and PPP3CA genes are involved in goat fecundity trait. Gene ontology enrichment analysis revealed that several biological pathways could be involved in the variation of fecundity in female goats. Conclusions: The identified significant SNPs or genes provide useful information about the underlying genetic control of fecundity trait which will be helpful to use them in goat breeding programs for improving the reproductive efficiency of goats. [ABSTRACT FROM AUTHOR]

Rice false smut (RFS), caused by Ustilaginoidea virens, is one of the most destructive grain diseases in rice production worldwide. Hence, to increase the ability of rice resistance to U. virens is a major breeding goal of rice breeders. However, it is difficult to evaluate rice resistance to U. virens. Hence, to clarify the RFS-resistance genetic mechanism is of great significance. In this study, a diversity panel landrace comprising of 315 accessions was identified for resistance against U. virens at reproductive stage in 2017 and 2018. Totally, 58 significant SNPs were distributed on the rice whole genome except chromosome 7, and 3 SNPs associated with three RFS-related traits were identified in 2 years. Haplotype block structure analysis predicted that a total of 15 candidate genes for U. virens resistance were screened based on significant SNPs with minimum P value (− log10P = 13.86). Of which, LOC_Os01g15580, a plant NBS-LRR protein coding gene near the significant SNP chr01_8738751 (12.3 kb), was considered a candidate for key resistance factor in the disease. These findings might provide a new insight into the genetic basis of resistance to rice false smut. [ABSTRACT FROM AUTHOR]

Background: In genetic analyses, the term 'batch effect' refers to systematic differences caused by batch heterogeneity. Controlling this unintended effect is the most important step in quality control (QC) processes that precede analyses. Currently, batch effects are not appropriately controlled by statistics, and newer approaches are required. Methods: In this report, we propose a new method to detect the heterogeneity of probe intensities among different batches and a procedure for calling genotypes and QC in the presence of a batch effect. First, we conducted a multivariate analysis of variance (MANOVA) to test the differences in probe intensities among batches. If heterogeneity is detected, subjects should be clustered using a K-medoid algorithm using the averages of the probe intensity measurements for each batch and the genotypes of subjects in different clusters should be called separately. Results: The proposed method was used to assess genotyping data of 3619 subjects consisting of 1074 patients with Alzheimer's disease, 296 with mild cognitive impairment (MCI), and 1153 controls. The proposed method improves the accuracy of called genotypes without the need to filter a lot of subjects and SNPs, and therefore is a reasonable approach for controlling batch effects. Conclusions: We proposed a new strategy that detects batch effects with probe intensity measurement and calls genotypes in the presence of batch effects. The application of the proposed method to real data shows that it produces a balanced approach. Furthermore, the proposed method can be extended to various scenarios with a simple modification. [ABSTRACT FROM AUTHOR]

As an important and complex trait, inflorescence length (IL) of soybean [Glycine max (L.) Merr.] significantly affected seed yields. Therefore, elucidating molecular basis of inflorescence architecture, especially for IL, was important for improving soybean yield potentials. Longer IL meaned to have more pod and seed in soybean. Hence, increasing IL and improving yield are targets for soybean breeding. In this study, a association panel, comprising 283 diverse samples, was used to dissect the genetic basis of IL based on genome-wide association analysis (GWAS) and haplotype analysis. GWAS and haplotype analysis were conducted through high-throughout single-nucleotide polymorphisms (SNP) developed by SLAF-seq methodology. A total of 39, 057 SNPs (minor allele frequency ≥ 0.2 and missing data ≤ 10%) were utilized to evaluate linkage disequilibrium (LD) level in the tested association panel. A total of 30 association signals were identified to be associated with IL via GWAS. Among them, 13 SNPs were novel, and another 17 SNPs were overlapped or located near the linked regions of known quantitative trait nucleotide (QTN) with soybean seed yield or yield component. The functional genes, located in the 200-kb genomic region of each peak SNP, were considered as candidate genes, such as the cell division/ elongation, specific enzymes, and signaling or transport of specific proteins. These genes have been reported to participant in the regulation of IL. Ten typical long-IL lines and ten typical short-IL lines were re-sequencing, and then, six SNPs from five genes were obtained based on candidate gene-based association. In addition, 42 haplotypes were defined based on haplotype analysis. Of them, 11 haplotypes were found to regulate long IL (> 14 mm) in soybean. The identified 30 QTN with beneficial alleles and their candidate genes might be valuable for dissecting the molecular mechanisms of IL and further improving the yield potential of soybean. [ABSTRACT FROM AUTHOR]

The identification of human predisposition genes to severe forms of infectious diseases is important for understanding the mechanisms of pathogenesis, as well as for the detection of the risk groups. This will allow one to carry out targeted vaccination and preventive therapy. The most common approaches to the genetic risk estimation include conducting association studies, in which the groups of patients and control individuals are compared using both preliminarily selected candidate genes and using genome-wide analysis. To search for genetic variants predisposed to severe forms of infectious diseases, it is expedient to form a control that consists of patients with clinically proven infections with asymptomatic or mild forms of the disease. The examples of the use of these approaches to identify genetic factors that predispose one to severe forms of infections caused by viruses from the Flaviviridae family are considered in the review. At present, a number of genetic markers associated with predisposition to tick-borne encephalitis, West Nile fever, and Dengue fever have already been detected. These associations must be confirmed in independent samples. Genetic variants, for which the association with spontaneous recovery during infection with hepatitis C virus, patient’s reaction on antiviral drugs, and the development of liver fibrosis was established, were also detected. The gene variants with more pronounced phenotypic effects will probably be found during further studies; they can be used in clinical practice as prognostic markers of the course and outcomes of infection with the Flaviviridae, as well as of the response to treatment. [ABSTRACT FROM AUTHOR]

Objective: To explore susceptibility genes associated with yang-deficiency constitution using single nucleotide polymorphism (SNP) genotyping. Methods: Based on an epidemiological survey, 30 volunteers with yang-deficiency constitution and 30 volunteers with a balanced constitution were included according to the Classification and Determination Standards of Constitutions in Traditional Chinese Medicine. Peripheral blood was collected and DNA was extracted from white blood cells. A genome-wide association study (GWAS) was conducted by SNP 6.0 genotyping at the Beijing CapitalBio Corporation Ltd. A minimum association P-value (Fisher's exact value) of less than 10 in the allele, genotype, dominant, and recessive models served as the standard for significant association of SNP with yang-deficiency constitution. Results: Among the four genetic models, a total of 42 SNPs were significantly associated with yang-deficiency constitution (Fisher's exact P-values P<10). These SNPs were adjacent to more than 20 genes, including RGS6, mGluR5, GAPDHL19, and IKZF1. Conclusion: Yang-deficiency constitution exhibits the characteristics of polygenic inheritance. This pilot study suggests that the polymorphisms in RGS6, mGluR5, GAPDHL19, and IKZF1 are associated with changes in cyclic adenosine monophosphate and cyclic guanosine monophosphate levels, memory, metabolic energy status, and immune function, respectively in people with yang-deficiency constitution. [ABSTRACT FROM AUTHOR]

Recent genome-wide association studies (GWAS) have implicated a range of genes from discrete biological pathways in the aetiology of autism. However, despite the strong influence of genetic factors, association studies have yet to identify statistically robust, replicated major effect genes or SNPs. We apply the principle of the SNP ratio test methodology described by O'Dushlaine et al to over 2100 families from the Autism Genome Project (AGP). Using a two-stage design we examine association enrichment in 5955 unique gene-ontology classifications across four groupings based on two phenotypic and two ancestral classifications. Based on estimates from simulation we identify excess of association enrichment across all analyses. We observe enrichment in association for sets of genes involved in diverse biological processes, including pyruvate metabolism, transcription factor activation, cell-signalling and cell-cycle regulation. Both genes and processes that show enrichment have previously been examined in autistic disorders and offer biologically plausibility to these findings. [ABSTRACT FROM AUTHOR]

Recently, single-nucleotide polymorphisms near the IL28B gene have been identified as important in predicting treatment response and spontaneous clearance of the hepatitis C virus (HCV). In the less than 12 months since the initial genetic discoveries, our knowledge base has rapidly expanded regarding the significance of the IL28B polymorphism in a variety of clinical settings. For genotype 1 HCV infection, it is clear that IL28B genotype has an important role in the prediction of treatment-induced and spontaneous clearance. This association remains important in the HIV/HCV-coinfected population. Host genotype adds further discriminatory information in HCV genotype 2/3 infection. IL28B genotype may remain significant with direct-acting antiviral therapy, although further studies are needed for antiviral agents and novel immunotherapy. Information on IL28B genotype improves treatment prediction with standard of care and will integrate with existing pretreatment clinical factors and measures of on-treatment response. Pretreatment knowledge of sustained viral response may help to reshape treatment regimens of the future with the possibility of reducing therapy duration and improving tolerability, safety, and efficacy. [ABSTRACT FROM AUTHOR]

To identify the genomic regions that confer risk and protection for major depressive disorder (MDD) in humans, large-scale studies are needed. Such studies should collect multiple phenotypes, DNA, and ideally, biological material that allows gene expression analysis, transcriptomic, proteomic, and metabolomic studies. In this paper, we briefly review linkage studies of MDD and then describe the large-scale nationwide biological sample collection in Dutch twin families from the Netherlands Twin Register (NTR) and in participants in the Netherlands Study of Depression and Anxiety (NESDA). Within these studies, 1862 participants with a diagnosis of MDD and 1857 controls at low liability for MDD have been selected for genome-wide genotyping by the US Foundation for the National Institutes of Health Genetic Association Information Network. Stage 1 genome-wide association results are scheduled to be accessible before the end of 2007. Genome-wide association results are open-access and can be viewed at the dbGAP web portal (http://www.ncbi.nlm.nih.gov). Approved users can download the genotype and phenotype data, which have been made available as of 9 October 2007.European Journal of Human Genetics (2008) 16, 335–342; doi:10.1038/sj.ejhg.5201979; published online 16 January 2008 [ABSTRACT FROM AUTHOR]