GWAS determined genetic loci associated with callus induction in oil palm tissue culture.

KEY MESSAGE: GWAS identified six loci at 25 kb downstream of WAK2, a crucial gene for cell wall and callus formation, enabling development of a SNP marker for enhanced callus induction potential. Efficient callus induction is vital for successful oil palm tissue culture, yet identifying genomic loci and markers for early detection of genotypes with high potential of callus induction remains unclear. In this study, immature male inflorescences from 198 oil palm accessions (dura, tenera and pisifera) were used as explants for tissue culture. Callus induction rates were collected at one-, two- and three-months after inoculation (C1, C2 and C3) as phenotypes. Resequencing generated 11,475,258 high quality single nucleotide polymorphisms (SNPs) as genotypes. GWAS was then performed, and correlation analysis revealed a positive association of C1 with both C2 (R = 0.81) and C3 (R = 0.50), indicating that C1 could be used as the major phenotype for callus induction rate. Therefore, only significant SNPs (P ≤ 0.05) in C1 were identified to develop markers for screening individuals with high potential of callus induction. Among 21 significant SNPs in C1, LD block analysis revealed six SNPs on chromosome 12 (Chr12) potentially linked to callus formation. Subsequently, 13 SNP markers were identified from these loci and electrophoresis results showed that marker C-12 at locus Chr12_12704856 can be used effectively to distinguish the GG allele, which showed the highest probability (69%) of callus induction. Furthermore, a rapid SNP variant detection method without electrophoresis was established via qPCR-based melting curve analysis. Our findings facilitated marker-assisted selection for specific palms with high potential of callus induction using immature male inflorescence as explant, aiding ortet palm selection in oil palm tissue culture.

postGWAS: A web server for deciphering the causality post the genome-wide association studies.

While genome-wide association studies (GWAS) have unequivocally identified vast disease susceptibility variants, a majority of them are situated in non-coding regions and are in high linkage disequilibrium (LD). To pave the way of translating GWAS signals to clinical drug targets, it is essential to identify the underlying causal variants and further causal genes. To this end, a myriad of post-GWAS methods have been devised, each grounded in distinct principles including fine-mapping, co-localization, and transcriptome-wide association study (TWAS) techniques. Yet, no platform currently exists that seamlessly integrates these diverse post-GWAS methodologies. In this work, we present a user-friendly web server for post-GWAS analysis, that seamlessly integrates 9 distinct methods with 12 models, categorized by fine-mapping, colocalization, and TWAS. The server mainly helps users decipher the causality hindered by complex GWAS signals, including casual variants and casual genes, without the burden of computational skills and complex environment configuration, and provides a convenient platform for post-GWAS analysis, result visualization, facilitating the understanding and interpretation of the genome-wide association studies. The postGWAS server is available at http://g2g.biographml.com/.

Genome-wide classification of epigenetic activity reveals regions of enriched heritability in immune-related traits.

Epigenetics underpins the regulation of genes known to play a key role in the adaptive and innate immune system (AIIS). We developed a method, EpiNN, that leverages epigenetic data to detect AIIS-relevant genomic regions and used it to detect 2,765 putative AIIS loci. Experimental validation of one of these loci, DNMT1, provided evidence for a novel AIIS-specific transcription start site. We built a genome-wide AIIS annotation and used linkage disequilibrium (LD) score regression to test whether it predicts regional heritability using association statistics for 176 traits. We detected significant heritability effects (average |τ∗|=1.65) for 20 out of 26 immune-relevant traits. In a meta-analysis, immune-relevant traits and diseases were 4.45× more enriched for heritability than other traits. The EpiNN annotation was also depleted of trans-ancestry genetic correlation, indicating ancestry-specific effects. These results underscore the effectiveness of leveraging supervised learning algorithms and epigenetic data to detect loci implicated in specific classes of traits and diseases.

CoreSNP: an efficient pipeline for core marker profile selection from genome-wide SNP datasets in crops.

BACKGROUND: DNA marker profiles play a crucial role in the identification and registration of germplasm, as well as in the distinctness, uniformity, and stability (DUS) testing of new plant variety protection. However, selecting minimal marker sets from large-scale SNP dataset can be challenging to distinguish a maximum number of samples. RESULTS: Here, we developed the CoreSNP pipeline using a "divide and conquer" strategy and a "greedy" algorithm. The pipeline offers adjustable parameters to guarantee the distinction of each sample pair with at least two markers. Additionally, it allows datasets with missing loci as input. The pipeline was tested in barley, soybean, wheat, rice and maize. A few dozen of core SNPs were efficiently selected in different crops with SNP array, GBS, and WGS dataset, which can differentiate thousands of individual samples. The core SNPs were distributed across all chromosomes, exhibiting lower pairwise linkage disequilibrium (LD) and higher polymorphism information content (PIC) and minor allele frequencies (MAF). It was shown that both the genetic diversity of the population and the characteristics of the original dataset can significantly influence the number of core markers. In addition, the core SNPs capture a certain level of the original population structure. CONCLUSIONS: CoreSNP is an efficiency way of core marker sets selection based on Genome-wide SNP datasets of crops. Combined with low-density SNP chip or genotyping technologies, it can be a cost-effective way to simplify and expedite the evaluation of genetic resources and differentiate different crop varieties. This tool is expected to have great application prospects in the rapid comparison of germplasm and intellectual property protection of new varieties.

X-Chromosome Association Study in Latin American Cohorts Identifies New Loci in Parkinson's Disease.

BACKGROUND: Sex differences in Parkinson's disease (PD) risk are well-known. However, the role of sex chromosomes in the development and progression of PD is still unclear. OBJECTIVE: The objective of this study was to perform the first X-chromosome-wide association study for PD risk in a Latin American cohort. METHODS: We used data from three admixed cohorts: (1) Latin American Research consortium on the Genetics of Parkinson's Disease (n = 1504) as discover cohort, and (2) Latino cohort from International Parkinson Disease Genomics Consortium (n = 155) and (3) Bambui Aging cohort (n = 1442) as replication cohorts. We also developed an X-chromosome framework specifically designed for admixed populations. RESULTS: We identified eight linkage disequilibrium regions associated with PD. We replicated one of these regions (top variant rs525496; discovery odds ratio [95% confidence interval]: 0.60 [0.478-0.77], P = 3.13 × 10-5 replication odds ratio: 0.60 [0.37-0.98], P = 0.04). rs5525496 is associated with multiple expression quantitative trait loci in brain and non-brain tissues, including RAB9B, H2BFM, TSMB15B, and GLRA4, but colocalization analysis suggests that rs5525496 may not mediate risk by expression of these genes. We also replicated a previous X-chromosome-wide association study finding (rs28602900), showing that this variant is associated with PD in non-European populations. CONCLUSIONS: Our results reinforce the importance of including X-chromosome and diverse populations in genetic studies. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

A weakly structured stem for human origins in Africa.

Despite broad agreement that Homo sapiens originated in Africa, considerable uncertainty surrounds specific models of divergence and migration across the continent1. Progress is hampered by a shortage of fossil and genomic data, as well as variability in previous estimates of divergence times1. Here we seek to discriminate among such models by considering linkage disequilibrium and diversity-based statistics, optimized for rapid, complex demographic inference2. We infer detailed demographic models for populations across Africa, including eastern and western representatives, and newly sequenced whole genomes from 44 Nama (Khoe-San) individuals from southern Africa. We infer a reticulated African population history in which present-day population structure dates back to Marine Isotope Stage 5. The earliest population divergence among contemporary populations occurred 120,000 to 135,000 years ago and was preceded by links between two or more weakly differentiated ancestral Homo populations connected by gene flow over hundreds of thousands of years. Such weakly structured stem models explain patterns of polymorphism that had previously been attributed to contributions from archaic hominins in Africa2-7. In contrast to models with archaic introgression, we predict that fossil remains from coexisting ancestral populations should be genetically and morphologically similar, and that only an inferred 1-4% of genetic differentiation among contemporary human populations can be attributed to genetic drift between stem populations. We show that model misspecification explains the variation in previous estimates of divergence times, and argue that studying a range of models is key to making robust inferences about deep history.

Evidence of epistasis in regions of long-range linkage disequilibrium across five complex diseases in the UK Biobank and eMERGE datasets.

Leveraging linkage disequilibrium (LD) patterns as representative of population substructure enables the discovery of additive association signals in genome-wide association studies (GWASs). Standard GWASs are well-powered to interrogate additive models; however, new approaches are required for invesigating other modes of inheritance such as dominance and epistasis. Epistasis, or non-additive interaction between genes, exists across the genome but often goes undetected because of a lack of statistical power. Furthermore, the adoption of LD pruning as customary in standard GWASs excludes detection of sites that are in LD but might underlie the genetic architecture of complex traits. We hypothesize that uncovering long-range interactions between loci with strong LD due to epistatic selection can elucidate genetic mechanisms underlying common diseases. To investigate this hypothesis, we tested for associations between 23 common diseases and 5,625,845 epistatic SNP-SNP pairs (determined by Ohta's D statistics) in long-range LD (>0.25 cM). Across five disease phenotypes, we identified one significant and four near-significant associations that replicated in two large genotype-phenotype datasets (UK Biobank and eMERGE). The genes that were most likely involved in the replicated associations were (1) members of highly conserved gene families with complex roles in multiple pathways, (2) essential genes, and/or (3) genes that were associated in the literature with complex traits that display variable expressivity. These results support the highly pleiotropic and conserved nature of variants in long-range LD under epistatic selection. Our work supports the hypothesis that epistatic interactions regulate diverse clinical mechanisms and might especially be driving factors in conditions with a wide range of phenotypic outcomes.

Interchromosomal linkage disequilibrium and linked fitness cost loci associated with selection for herbicide resistance.

The adaptation of weeds to herbicide is both a significant problem in agriculture and a model of rapid adaptation. However, significant gaps remain in our knowledge of resistance controlled by many loci and the evolutionary factors that influence the maintenance of resistance. Here, using herbicide-resistant populations of the common morning glory (Ipomoea purpurea), we perform a multilevel analysis of the genome and transcriptome to uncover putative loci involved in nontarget-site herbicide resistance (NTSR) and to examine evolutionary forces underlying the maintenance of resistance in natural populations. We found loci involved in herbicide detoxification and stress sensing to be under selection and confirmed that detoxification is responsible for glyphosate (RoundUp) resistance using a functional assay. We identified interchromosomal linkage disequilibrium (ILD) among loci under selection reflecting either historical processes or additive effects leading to the resistance phenotype. We further identified potential fitness cost loci that were strongly linked to resistance alleles, indicating the role of genetic hitchhiking in maintaining the cost. Overall, our work suggests that NTSR glyphosate resistance in I. purpurea is conferred by multiple genes which are potentially maintained through generations via ILD, and that the fitness cost associated with resistance in this species is likely a by-product of genetic hitchhiking.

Association between the ELAVL1 gene single nucleotide polymorphisms and the Genetic Susceptibility to cervical cancer by high resolution melting in a Tunisian population.

BACKGROUND: Human papillomavirus is the major cause of cervical cancer, but only few cases develop into cancer. Nevertheless, HuR (ELAVL1) gene has been implicated in the oncogenesis of certain cancers. The correlation between ELAVL1 gene and the risk of cervical cancer remains unclear. Therefore, this study investigated the effect of ELAVL1 gene polymorphisms (SNPs) in cervical cancer development in Tunisian women. METHOD: ELAVL1 gene SNPs: ELAVL1 rs12983784 T > C, ELAVL1 rs14394 T > C, ELAVL1 rs74369359 G > T, ELAVL1 rs35986520 G > A, ELAVL1 rs10402477 C > T, ELAVL1 rs12985234 A > G and ELAVL1 rs2042920 T > G, were genotyped by High resolution melting (HRM). SNPStats software was used to perform linkage disequilibrium (LD) and haplotype analysis. RESULTS: Comparing the cervical cancer patients with healthy control participants, the SNPs rs12983784 (P = 0.032), rs74369359 (p = < 10- 3) and rs10402477 (P = 0.001) were associated with an increased cervical cancer risk. Contrary to the SNPs rs14394, rs7469359, rs35986520, rs12985234 and rs2042920 (p˃0.05). The haplotype analysis of the seven SNPs of ELAVL1 gene showed that there is no association between the different haplotypes and a possible risk of cervical cancer disease. Moreover, there was a significant Linkage disequilibrium between rs35986520 and rs2042920 (D'=0.9972) and between rs2042920 and rs10402477 (D'=0.9977). CONCLUSION: Our results indicated that genetic variants in the ELAVL1 gene might be associated with susceptibility to cervical cancer in the Tunisian population.

An overview of genome-wide association mapping studies in Poaceae species (model crops: wheat and rice).

There is a significant interest while utilizing association mapping technique to determine the genes which are accountable for numerical dissimilarity of the more complex characteristics with agronomic and evolutionary significance. Recently improvements have been made in genomic technology, which motivates for the exploitation of natural diversity, and establishment of more vigorous and strong statistical analysis methods. It creates association mapping technique more demanding and reasonable to plant research programs. Genome-wide association mapping technique recognizes quantitative trait loci (QTLs) by studying the marker-trait associations which could be credited to the power of linkage disequilibrium between different molecular markers and functional polymorphisms through a pool of diversified germplasm. In this review, we will describe an overview of genetic mapping and the current status of association mapping studies in model cereal crops i.e., wheat and rice.

A saturated map of common genetic variants associated with human height.

Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel2) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries.

The evolutionary patterns of barley pericentromeric chromosome regions, as shaped by linkage disequilibrium and domestication.

The distribution of recombination events along large cereal chromosomes is uneven and is generally restricted to gene-rich telomeric ends. To understand how the lack of recombination affects diversity in the large pericentromeric regions, we analysed deep exome capture data from a final panel of 815 Hordeum vulgare (barley) cultivars, landraces and wild barleys, sampled from across their eco-geographical ranges. We defined and compared variant data across the pericentromeric and non-pericentromeric regions, observing a clear partitioning of diversity both within and between chromosomes and germplasm groups. Dramatically reduced diversity was found in the pericentromeres of both cultivars and landraces when compared with wild barley. We observed a mixture of completely and partially differentiated single-nucleotide polymorphisms (SNPs) between domesticated and wild gene pools, suggesting that domesticated gene pools were derived from multiple wild ancestors. Patterns of genome-wide linkage disequilibrium, haplotype block size and number, and variant frequency within blocks showed clear contrasts among individual chromosomes and between cultivars and wild barleys. Although most cultivar chromosomes shared a single major pericentromeric haplotype, chromosome 7H clearly differentiated the two-row and six-row types associated with different geographical origins. Within the pericentromeric regions we identified 22 387 non-synonymous SNPs, 92 of which were fixed for alternative alleles in cultivar versus wild accessions. Surprisingly, only 29 SNPs found exclusively in the cultivars were predicted to be 'highly deleterious'. Overall, our data reveal an unconventional pericentromeric genetic landscape among distinct barley gene pools, with different evolutionary processes driving domestication and diversification.

Functional characterization of the schizophrenia associated gene AS3MT identifies a role in neuronal development.

Genome-wide association studies (GWAS) have identified multiple genomic regions associated with schizophrenia, although many variants reside in noncoding regions characterized by high linkage disequilibrium (LD) making the elucidation of molecular mechanisms challenging. A genomic region on chromosome 10q24 has been consistently associated with schizophrenia with risk attributed to the AS3MT gene. Although AS3MT is hypothesized to play a role in neuronal development and differentiation, work to fully understand the function of this gene has been limited. In this study we explored the function of AS3MT using a neuronal cell line (SH-SY5Y). We confirm previous findings of isoform specific expression of AS3MT during SH-SY5Y differentiation toward neuronal fates. Using CRISPR-Cas9 gene editing we generated AS3MT knockout SH-SY5Y cell lines and used RNA-seq to identify significant changes in gene expression in pathways associated with neuronal development, inflammation, extracellular matrix formation, and RNA processing, including dysregulation of other genes strongly implicated in schizophrenia. We did not observe any morphological changes in cell size and neurite length following neuronal differentiation and MAP2 immunocytochemistry. These results provide novel insights into the potential role of AS3MT in brain development and identify pathways through which genetic variation in this region may confer risk for schizophrenia.

TOP-LD: A tool to explore linkage disequilibrium with TOPMed whole-genome sequence data.

Current publicly available tools that allow rapid exploration of linkage disequilibrium (LD) between markers (e.g., HaploReg and LDlink) are based on whole-genome sequence (WGS) data from 2,504 individuals in the 1000 Genomes Project. Here, we present TOP-LD, an online tool to explore LD inferred with high-coverage (∼30×) WGS data from 15,578 individuals in the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. TOP-LD provides a significant upgrade compared to current LD tools, as the TOPMed WGS data provide a more comprehensive representation of genetic variation than the 1000 Genomes data, particularly for rare variants and in the specific populations that we analyzed. For example, TOP-LD encompasses LD information for 150.3, 62.2, and 36.7 million variants for European, African, and East Asian ancestral samples, respectively, offering 2.6- to 9.1-fold increase in variant coverage compared to HaploReg 4.0 or LDlink. In addition, TOP-LD includes tens of thousands of structural variants (SVs). We demonstrate the value of TOP-LD in fine-mapping at the GGT1 locus associated with gamma glutamyltransferase in the African ancestry participants in UK Biobank. Beyond fine-mapping, TOP-LD can facilitate a wide range of applications that are based on summary statistics and estimates of LD. TOP-LD is freely available online.

Development of novel polymorphic microsatellite markers for Picea brachytyla.

BACKGROUND: Picea brachytyla is a unique tree species in China. Due to being extensively exploited in the past, it is listed as Vulnerable in the IUCN Red List. It is mainly distributed across the Hengduan and Daba-Qinglin mountains and has been found in other areas including Sichuan Province and Qinghai Province, China. Microsatellites, or simple sequence repeats (SSRs), are widely used in correlational studies of genetic protection. Few markers have been developed for P. brachytyla because of the small number of trees and scholarly resources available for study. METHODS AND RESULTS: The genomic DNA of P. brachytyla was sequenced using the DNBSEQ platform, and unigenes were obtained after assembly and deredundancy. Of the 100 primer pairs screened, we isolated 10 useful microsatellite loci from P. brachytyla genes. The observed and expected heterozygosity values ranged from 0.173 (P24) to 0.788 (P79; mean 0.469) and 0.199 (P87) to 0.911 (P79; mean 0.700), respectively. Polymorphism-information content (PIC) ranged from 0.190 (P84) to 0.904 (P79; mean 0.666). Only P84 and P72 were in a Hardy-Weinberg equilibrium (P > 0.05) in the different P. brachytyla populations. All the levels of linkage disequilibrium (LD) were high for the 10 SSR loci indicating that there were no autocorrelations among the 10 SSR loci. CONCLUSIONS: The novel polymorphic microsatellite markers showed high polymorphism for P. brachytyla. These polymorphic microsatellites can provide a basis for future conservation and genetic research on this rare plant species.

Recombination and mutation shape variations in the major histocompatibility complex.

The major histocompatibility complex (MHC) is closely associated with numerous diseases, but its high degree of polymorphism complicates the discovery of disease-associated variants. In principle, recombination and de novo mutations are two critical factors responsible for MHC polymorphisms. However, direct evidence for this hypothesis is lacking. Here, we report the generation of fine-scale MHC recombination and de novo mutation maps of ∼5 Mb by deep sequencing (> 100×) of the MHC genome for 17 MHC recombination and 30 non-recombination Han Chinese families (a total of 190 individuals). Recombination hotspots and Han-specific breakpoints are located in close proximity at haplotype block boundaries. The average MHC de novo mutation rate is higher than the genome-wide de novo mutation rate, particularly in MHC recombinant individuals. Notably, mutation and recombination generated polymorphisms are located within and outside linkage disequilibrium regions of the MHC, respectively, and evolution of the MHC locus was mainly controlled by positive selection. These findings provide insights on the evolutionary causes of the MHC diversity and may facilitate the identification of disease-associated genetic variants.

Shared genomic architecture between COVID-19 severity and numerous clinical and physiologic parameters revealed by LD score regression analysis.

The COVID-19 pandemic has produced broad clinical manifestations, from asymptomatic infection to hospitalization and death. Despite progress from genomic and clinical epidemiology research, risk factors for developing severe COVID-19 are incompletely understood and identification of modifiable risk factors is desperately needed. We conducted linkage disequilibrium score regression (LDSR) analysis to estimate cross-trait genetic correlation between COVID-19 severity and various polygenic phenotypes. To attenuate the genetic contribution of smoking and BMI, we further conducted sensitivity analyses by pruning genomic regions associated with smoking/BMI and repeating LDSR analyses. We identified robust positive associations between the genetic architecture of severe COVID-19 and both BMI and smoking. We observed strong positive genetic correlation (rg) with diabetes (rg = 0.25) and shortness of breath walking on level ground (rg = 0.28) and novel protective associations with vitamin E (rg = - 0.53), calcium (rg = - 0.33), retinol (rg = - 0.59), Apolipoprotein A (rg = - 0.13), and HDL (rg = - 0.17), but no association with vitamin D (rg = - 0.02). Removing genomic regions associated with smoking and BMI generally attenuated the associations, but the associations with nutrient biomarkers persisted. This study provides a comprehensive assessment of the shared genetic architecture of COVID-19 severity and numerous clinical/physiologic parameters. Associations with blood and plasma-derived traits identified biomarkers for Mendelian randomization studies to explore causality and nominates therapeutic targets for clinical evaluation.

Epigenomic and Transcriptomic Prioritization of Candidate Obesity-Risk Regulatory GWAS SNPs.

Concern about rising rates of obesity has prompted searches for obesity-related single nucleotide polymorphisms (SNPs) in genome-wide association studies (GWAS). Identifying plausible regulatory SNPs is very difficult partially because of linkage disequilibrium. We used an unusual epigenomic and transcriptomic analysis of obesity GWAS-derived SNPs in adipose versus heterologous tissues. From 50 GWAS and 121,064 expanded SNPs, we prioritized 47 potential causal regulatory SNPs (Tier-1 SNPs) for 14 gene loci. A detailed examination of seven loci revealed that four (CABLES1, PC, PEMT, and FAM13A) had Tier-1 SNPs positioned so that they could regulate use of alternative transcription start sites, resulting in different polypeptides being generated or different amounts of an intronic microRNA gene being expressed. HOXA11 and long noncoding RNA gene RP11-392O17.1 had Tier-1 SNPs in their 3' or promoter region, respectively, and strong preferences for expression in subcutaneous versus visceral adipose tissue. ZBED3-AS1 had two intragenic Tier-1 SNPs, each of which could contribute to mediating obesity risk through modulating long-distance chromatin interactions. Our approach not only revealed especially credible novel regulatory SNPs, but also helped evaluate previously highlighted obesity GWAS SNPs that were candidates for transcription regulation.

Polymorphisms of the filaggrin gene are associated with atopic dermatitis in the Caucasian population of Central Russia.

Association of the filaggrin (FLG) gene with atopic dermatitis (AD) in Caucasians from Central Russia was studied in the sample of 700 patients and 612 controls. In total ten SNPs of the gene (rs61816761, rs12130219, rs77199844, rs558269137, rs4363385, rs12144049, rs471144, rs6661961, rs10888499, rs3126085), their haplotypes and interlocus interactions were analyzed using logistic regression. The functional effects of the AD risk candidate loci and their proxies (136 SNPs) were evaluated by in silico analysis. All analyzed SNPs were associated with AD: two SNPs (rs3126085 and rs12144049) manifested the independent association, nine SNPs were associated within 30 haplotypes, and seven SNPs showed interlocus interaction effects within ten most significant epistatic models. Alleles A rs3126085 and C rs12144049 were associated with a higher risk of AD according to the allelic (ORs being 1.75, pperm = 0.002 and 1.45, pperm = 0.011 respectively), additive (ORs being 1.69, pperm = 0.004 and 1.47, pperm = 0.011 respectively) and dominant (ORs being 1.79, pperm = 0.004 and 1.63, pperm = 0.005 respectively) genetic models. Three haplotypes, GT[rs3126085-rs12144049] (OR = 0.60), GGT[rs61816761-rs3126085-rs12144049] (OR = 0.59), and AWGGT[rs12130219-rs558269137-rs61816761-rs3126085-rs12144049] (OR = 0.63) demonstrated the protective effect (pperm = 0.001). The in silico analysis suggested that the AD risk variants and their proxies apparently produce various effects on 38 genes in various tissue/organs (including 20 genes in the skin). The biological process enrichment analyses suggest that the target AD candidate genes influence the formation of the cornified envelope, keratinization and cornification, and more than twenty other pathways related to skin development, programmed cell death, and regulation of water loss via skin.

Genome-wide association mapping for high temperature tolerance in wheat through 90k SNP array using physiological and yield traits.

Dissecting the genetic basis of physiological and yield traits against tolerance to heat stress is an essential in wheat breeding programs to boost up the wheat yield for sustainable food security. Herein, a genome-wide association study (GWAS) was performed to reveal the genetic basis of heat tolerance using high-density Illumina 90K Infinium SNPs array through physiological and yield indices. These indices were phenotyped on a diverse panel of foreign and domestic genotypes of Pakistan, grown in normal and heat-stressed environments. Based on STRUCTURE analysis, the studied germplasm clustered into four sub-population. Highly significant variations with a range of moderate (58.3%) to high (77.8%) heritability was observed under both conditions. Strong positive correlation existed among physiological and yield related attributes. A total of 320 significant (-log10 P ≥ 3) marker-trait associations (MTAs) were identified for the observed characters. Out of them 169 and 151 MTAs were recorded in normal and heat stress environments, respectively. Among the MTA loci, three (RAC875_c103017_302, Tdurum_contig42087_1199, and Tdurum_contig46877_488 on chromosomes 4B, 6B, and 7B respectively), two (BobWhite_c836_422 and BS00010616_51) and three (Kukri_rep_c87210_361, D_GA8KES401BNLTU_253 and Tdurum_contig1015_131) on chromosomes 5A, 1B, and 3D at the positions 243.59cM, 77.82cM and 292.51cM) showed pleiotropic effects in studied traits under normal, heat-stressed and both conditions respectively. The present study not only authenticated the numerous previously reported MTAs for examined attributes but also revealed novel MTAs under heat-stressed conditions. Identified SNPs will be beneficial in determining the novel genes in wheat to develop the heat tolerant and best yielded genotypes to fulfill the wheat requirement for the growing population.