Biology subjects

Yang, Y.

Publications and source records attributed to Yang, Y..

At least 1,369 records · Page 76Linked to original sources

bioRxiv2018

Anterior insular cortex plays a critical role in interoceptive attention

Although accumulating evidence indicates that the anterior insular cortex (AIC) mediates interoceptive attention, which refers the attention towards physiological signals arising from the body, the necessity of the AIC in this process has not been demonstrated. Using a novel task that directs attention toward breathing rhythm, we assessed the involvement of the AIC in interoceptive attention in healthy participants using functional magnetic resonance imaging and examined the necessity of the AIC in interoceptive attention in patients with AIC lesions. We found that interoceptive attention was associated with greater AIC activation, as well as enhanced coupling between the AIC and somatosensory area along with reduced coupling between AIC and visual sensory areas. AIC activation and connectivity were predictive of individual differences in interoceptive accuracy. Importantly, AIC lesion patients showed disrupted interoceptive discrimination accuracy and sensitivity. Together, these results provide compelling evidence that AIC plays a critical role in interoceptive attention.

neuroscience↗

bioRxiv2018

Pre-implantation genetic diagnosis for a family with Usher syndrome through targeted sequencing and haplotype analysis

ObjectiveOur objective was to investigate the applicability of targeted capture massively parallel sequencing in developing personalized pre-implantation genetic diagnosis (PGD) assay.\n\nMethodsOne couple at risk of transmitting Usher Syndrome to their offspring was recruited to this study. The genomics DNA (gDNA) was extracted from the peripheral blood and underwent in vitro fertilization (IVF)-PGD. Prenatal molecular diagnosis was performed in the 20th week of gestation and the chromosomal anomaly was analyzed.\n\nResultsCustomized capture probe targeted at USH2A gene and 350kb flanking region were designed for PGD. Eleven blastocysts were biopsied and amplified by using multiple displacement amplification (MDA) and capture sequencing. A HMM-based haplotype analysis was performed to deduce embryos genotype by using SNPs identified in each sample. Four embryos were diagnosed as free of fathers rare mutation, two were transferred and one achieved a successful pregnancy. The fetal genotype was confirmed by Sanger sequencing of fetal genomic DNA obtained by amniocentesis. The PGD and prenatal diagnosis results were further confirmed by the molecular diagnosis of the babys genomic DNA sample. The auditory test showed that the hearing was normal.\n\nConclusionTargeted capture massively parallel sequencing (MPS) is an effective and convenient strategy to develop customized PGD assay.\n\nKey pointsGenetic counseling session was conducted with a family having Usher patient who was molecularly diagnosed, and a healthy baby was born with the help of successful PGD assay. This is of vast importance in management plans since it is the first report of PGD in Usher syndrome based on targeted capture MPS.

genetics↗

bioRxiv2018

Sparse additive interaction learning

A conceptual paradigm for onset of a new disease is often considered to be the result of changes in entire biological networks whose states are affected by a complex interaction of genetic and environmental factors. However, when modelling a relevant phenotype as a function of high dimensional measurements, power to estimate interactions is low, the number of possible interactions could be enormous and their effects may be non-linear. In this work, we introduce a method called sail for detecting non-linear interactions with a key environmental or exposure variable in high-dimensional settings which respects the strong or weak heredity constraints. We prove that asymptotically, our method possesses the oracle property, i.e., it performs as well as if the true model were known in advance. We develop a computationally efficient fitting algorithm with automatic tuning parameter selection, which scales to high-dimensional datasets. Through an extensive simulation study, we show that sail outperforms existing penalized regression methods in terms of prediction accuracy and support recovery when there are non-linear interactions with an exposure variable. We apply sail to detect non-linear interactions between genes and a prenatal psychosocial intervention program on cognitive performance in children at 4 years of age. Results show that individuals who are genetically predisposed to lower educational attainment are those who stand to benefit the most from the intervention. Our algorithms are implemented in an R package available on CRAN (https://cran.r-project.org/package=sail).

bioinformatics↗

bioRxiv2018

Targeting RyR2 with a phosphorylation site-specific nanobody Reverses Dysfunction of Failing Cardiomyocytes in Rat

Chronic PKA phosphorylation of RyR2 has been shown to increased diastolic SR Ca2+ leak and lead to cardiac dysfunction. Since the change of phosphorylation level of RyR2 is a biomarker of failing heart, we attempted to verify the hypothesis that intracellular gene delivery of a RyR2 targeting phosphorylation site-specific nanobody could preserve contractility of failing myocardium. In present study, we acquired the RyR2-specific nanobodies from a phage display library which are variable domains of camellidae heavy chain-only antibodies (VHH). One of the monoclonal nanobodies, AR185, inhibiting RyR2 phosphorylation in an in vitro assay was then chosen for further investigation. We investigated the potential of adeno-associated virus (AAV)-9-mediated cardiac expression of AR185 against post-ischemic heart failure. Adeno-associated virus gene delivery elevated the intracellular expression AR185 protein in the ischemic heart failure model of rats, and this treatment normalized the systolic and diastolic dysfunction of the failing myocardium in vivo and in vitro by reversing myocardial Ca2+ handling. Furthermore, AR185 gene transfer to failing cardiomyocytes reduced the frequency of sarcoplasmic reticulum (SR) calcium leak, thereby restoring the attenuated intracellular calcium transients and SR calcium load. Moreover, AR185 gene transfer inhibited PKA phosphorylation of RyR2 in failing cardiomyocytes. Our results provided strong pre-clinical experimental evidence of the cardiac expression of RyR2 nanobody with AAV9 vectors as a promising therapeutic strategy for ischemic heart failure.

pathology↗

bioRxiv2018

Gating TrkB switch by methylglyoxal enables GLO1 as a target for depression

The endogenous metabolite methylglyoxal (MGO) has recently emerged as a potential mediator of psychiatric disorders, such as anxiety and depression, but its precise mechanism of action remains poorly understood. Here, we find that MGO concentrations are decreased in the prefrontal cortex and hippocampus in rats subjected to chronic stress, and low-dose MGO treatment remarkedly enhances resilience to stress and alleviates depression-like symptoms. This effect is achieved by MGOs promotion on the synaptic plasticity in prefrontal cortex and hippocampus. Both in vitro and in vivo experiments show that MGO provokes the dimerization and autophosphorylation of TrkB and the subsequent activation of downstream Akt/CREB signaling, which leads to a rapid and sustained expression of brain-derived neurotrophic factor (BDNF). We further demonstrate that MGO directly binds to the extracellular domain of TrkB, but not its intracellular domain. In addition, we also identify a natural product luteolin and its derivative lutD as potent inhibitors of Glyoxalase 1 and validate their antidepressant effects in chronic stress rat models. The antidepressant role of endogenous MGO provides a new basis for the understanding and therapeutic intervention design for stress-associated mental disorders.

neuroscience↗

bioRxiv2018

Deep learning light field microscopy for rapid four-dimensional imaging of behaving animals

Light-field microscopy has emerged as a technique of choice for high-speed volumetric imaging of fast biological processes. However, artefacts, non-uniform resolution, and a slow reconstruction speed have limited its full capabilities for in toto extraction of the dynamic spatiotemporal patterns in samples. Here, we combined a view-channel-depth (VCD) neural network with light-field microscopy to mitigate these limitations, yielding artefact-free three-dimensional image sequences with uniform spatial resolution and three-order-higher video-rate reconstruction throughput. We imaged neuronal activities across moving C. elegans and blood flow in a beating zebrafish heart at single-cell resolution with volume rates up to 200 Hz.

biophysics↗

bioRxiv2018

Atlas-CNV: a validated approach to call Single-Exon CNVs in the eMERGESeq gene panel

PurposeTo provide a validated method to confidently identify exon-containing copy number variants (CNVs), with a low false discovery rate (FDR), in targeted sequencing data from a clinical laboratory with particular focus on single-exon CNVs.\n\nMethodsDNA sequence coverage data are normalized within each sample and subsequently exonic CNVs are identified in a batch of samples (midpool), when the target log2 ratio of the sample to the batch median exceeds defined thresholds. The quality of exonic CNV calls is assessed by C-scores (Z-like scores) using thresholds derived from gold standard samples and simulation studies. We integrate an ExonQC threshold to lower FDR and compare performance with alternate software (VisCap).\n\nResultsThirteen CNVs were used as a truth set to validate Atlas-CNV and compared with VisCap. We demonstrated FDR reduction in validation, simulation and 10,926 eMERGESeq samples without sensitivity loss. Sixty-four multi-exon and 29 single-exon CNVs with high C-scores were assessed by MLPA.\n\nConclusionsAtlas-CNV is validated as a method to identify exonic CNVs in targeted sequencing data generated in the clinical laboratory. The ExonQC and C-score assignment can reduce FDR (identification of targets with high variance) and improve calling accuracy of single-exon CNVs respectively. We proposed guidelines and criteria to identify high confidence single-exon CNVs.

genomics↗

bioRxiv2018

5-Hydroxymethylcytosines from Circulating Cell-free DNA as Diagnostic and Prognostic Markers for Hepatocellular Carcinoma

The lack of highly sensitive and specific diagnostic biomarkers is a major contributor to the poor outcomes of patients with hepatocellular carcinoma (HCC), the second-most common cause of cancer deaths worldwide. We sought to develop a clinically convenient and minimally-invasive approach that can be deployed at scale for the sensitive, specific, and highly reliable diagnosis of HCC, and to evaluate the potential prognostic value of this approach. The study cohort comprised of 2,728 subjects, including HCC patients (n = 1,208), controls (n = 965) (572 healthy individuals and 393 patients with benign lesions), as well as patients with chronic hepatitis B infection (CHB) (n =291), liver cirrhosis (LC) (n = 110), and cholangiocarcinoma (CCC) (n = 154), was recruited from three major liver cancer hospitals in Shanghai, China, from July 2016 to November 2017. Circulating cell-free DNA (cfDNA) were collected from plasma samples from these individuals before surgery or any radical treatment. Applying our 5hmC-Seal technique, the summarized 5-hydroxymethylcytosine (5hmC) profiles in cfDNA were obtained. Molecular annotation analysis suggested that the profiled 5hmC loci in cfDNA were enriched with liver tissue-derived regulatory markers (e.g., H3K4me1). We showed that a weighted diagnostic score (wd-score) based on 117 genes detected using the summarized 5hmC profiles in cfDNA accurately distinguished HCC patients from controls (AUC = 95.1%; 95% CI, 93.6-96.5%) in the validation set, markedly outperformed -fetoprotein (AFP) with superior sensitivity. The wd-scores, which not only detected early BCLC stages (e.g., Stage 0: AUC = 96.2%; 95% CI,94.1-98.4%) and small tumors (e.g., < 2 cm: AUC = 95.7%; 95% CI: 93.6-97.7%), also showed high capacity for distinguishing HCC from non-cancer patients with CHB/LC (AUC = 80.2%; 95% CI, 75.8-84.6%). Moreover, the prognostic value of 5hmC markers in cfDNA was evaluated for HCC recurrence, showing that a weighted prognostic score (wp-score) based on 16 marker genes predicted the recurrence risk (HR = 6.67; 95% CI, 2.81-15.82, p < 0.0001) in 555 patients who have been followed up after surgery. In conclusion, we have developed and validated a robust 5hmC-based diagnostic model that can be applied routinely with clinically feasible amount of cfDNA (e.g., from ~2-5 mL of plasma). Applying this new approach in the clinic could significantly improve the clinical outcomes of HCC patients, for example by early detection of those patients with surgically resectable tumors or as a convenient disease surveillance tool for recurrence.

cancer biology↗

bioRxiv2018

Exploring spatio-temporal neural dynamics of the human visual cortex

The human visual cortex is organized in a hierarchical manner. Although a significant body of evidence has been accumulated in support of this hypothesis, specific details regarding the spatial and temporal information flow remain open. Here we present detailed spatio-temporal correlation profiles of neural activity with low-level and high-level features derived from a \"deep\" (8-layer) neural network pre-trained for object recognition. These correlation profiles indicate an early-to-late shift from low-level features to high-level features and from low-level regions to higher-level regions along the visual hierarchy, consistent with feedforward information flow. To refine our understanding of information flow, we computed three sets of features from the low-and high-level features provided by the neural network: object-category-relevant low-level features (the common components between low-level and high-level features), low-level features roughly orthogonal to high-level features (the residual Layer 1 features), and unique high-level features that were roughly orthogonal to low-level features (the residual Layer 7 features). Contrasting the correlation effects of the common components and the residual Layer 1 features, we observed that the early visual cortex exhibits a similar amount of correlation with the two feature sets early in time (60 to 120 ms), but in a later time window, the early visual cortex exhibits a higher and longer correlation effect with the common components/low-level task-relevant features as compared to the low-level residual features--an effect unlikely to arise from purely feedforward information flow. Overall, our results indicate that non-feedforward processes, for example, top-down influences from mental representations of categories, may facilitate differentiation between these two types of low-level features within the early visual cortex.

neuroscience↗

bioRxiv2018

A familial case of Syndactyly type IV due to a novel duplication of ~222.23 kb covering exons 2-17 of the LMBR1 gene: a case report

Syndactyly is one of the most frequent hereditary limb malformations with clinical and genetical complexity. Autosomal dominant Syndactyly type IV (SD4) is a very rare form of syndactyly, occurring as a result of heterozygous mutation in an SHH regulatory element (ZRS) that resides in intron 5 of the LMBR1 gene on chromosome 7q36.3. The SD4 is characterized by complete cutaneous syndactyly of all fingers, cup-shaped hands due to flexion of the fingers and accompanied by polydactyly. Here, we firstly reported a big Chinese family, manifesting cup-shaped hands consistent with SD4 and intrafamilial heterogeneity in clinical phenotype of tibial and fibulal shortening, triphalangeal thumb-polysyndactyly syndrome (TPTPS). Genetically, we identified a novel duplication of [~]222.23 kb covering exons 2-17 of the LMBR1 gene in this family by next generation sequencing. This case expands our new clinical understanding of SD4 phenotype.

genetics↗

bioRxiv2018

High-glucose Induces Retinal Pigment Epithelium Mitochondrial Pathways of Apoptosis and Inhibits Mitophagy by Regulating ROS/PINK1/Parkin Signal Pathway

Diabetic retinopathy (DR) caused visual performance degradation seriously endangers human beings health, uncovering the underlying mechanism might shed light on the discovery of DR therapeutic treatments. In this study, we found that the effects of glucose on retinal pigment epithelium (RPE) varies in a dose dependent manner, high-glucose promotes ROS generation and cell apoptosis, inhibits mitophagy as well as proliferative abilities, while low-glucose induces ROS production and cell mitophagy, but has little impacts on cell apoptosis and proliferation. Of note, the toxic effects of high-glucose on RPE are alleviated by ROS scavengers and aggravated by autophagy inhibitor 3-methyladenine (3-MA) or mitophagy inhibitor cyclosporin A (CsA). High-glucose induced ROS generation is merely eliminated by ROS scavengers instead of mitophagy or autophagy inhibitor. We also proved that high-glucose inhibits cell proliferation and promotes cell apoptosis by regulating ROS mediated inhibition of mitophagy. In addition, mitophagy associated proteins PINK1 and Parkin are downregulated by high-glucose or hydrogen peroxide treatments, which are reversed by ROS scavengers. Of note, Knock-down of PINK1 decreases phospharylated Parkin instead of total Parkin levels in RPE. Intriguingly, high-glucoses inhibiting effects on cell mitophagy as well as proliferation and its promoting effects on cell apoptosis are reversed by either PINK1 or Parkin overexpression. Therefore, we concluded that high-glucose promotes RPE apoptosis and inhibits cell proliferation as well as mitophagy by regulating oxidative stress mediated inactivation of ROS/PINKl/Parkin signal pathway.

cell biology↗

bioRxiv2018

Optimization of T-DNA architecture for Cas9-mediated mutagenesis in Arabidopsis

Bacterial CRISPR systems have been widely adopted to create operator-specified site-specific nucleases. Such nuclease action commonly results in loss-of-function alleles, facilitating functional analysis of genes and gene families We conducted a systematic comparison of components and T-DNA architectures for CRISPR-mediated gene editing in Arabidopsis, testing multiple promoters, terminators, sgRNA backbones and Cas9 alleles. We identified a T-DNA architecture that usually results in stable (i.e. homozygous) mutations in the first generation after transformation. Notably, the transcription of sgRNA and Cas9 in head-to-head divergent orientation usually resulted in highly active lines. Our Arabidopsis data may prove useful for optimization of CRISPR methods in other plants.

plant biology↗

bioRxiv2018

Utilisation of staphylococcal immune evasion protein Sbi as a novel vaccine adjuvant

Co-ligation of the B cell antigen receptor with complement receptor 2 on B-cells via a C3d-opsonised antigen complex significantly lowers the threshold required for B cell activation. Consequently, fusions of antigens with C3d polymers have shown great potential in vaccine design. However, these linear arrays of C3d multimers do not mimic the natural opsonisation of antigens with C3d. Here we investigate the potential of using the unique complement activating characteristics of Staphylococcal immune-evasion protein Sbi to develop a pro-vaccine approach that spontaneously coats antigens with C3 degradation products in a natural way. We show that Sbi rapidly triggers the alternative complement pathway through recruitment of complement regulators, forming a tripartite complex that acts as a competitive antagonist of factor H, resulting in enhanced complement consumption. These functional results are corroborated by the structure of this complement activating Sbi-III-IV:C3d:FHR-1 complex. Finally, we demonstrate that Sbi, fused with Mycobacterium tuberculosis antigen Ag85b, causes efficient opsonisation with C3 fragments, thereby enhancing the immune response significantly beyond that of Ag85b alone, providing proof of concept for our pro-vaccine approach.

biochemistry↗

bioRxiv2018

MAPS: model-based analysis of long-range chromatin interactions from PLAC-seq and HiChIP experiments

Hi-C and chromatin immunoprecipitation (ChIP) have been combined to identify long-range chromatin interactions genome-wide at reduced cost and enhanced resolution, but extracting the information from the resulting datasets has been challenging. Here we describe a computational method, MAPS, Model-based Analysis of PLAC-seq and HiChIP, to process the data from such experiments and identify long-range chromatin interactions. MAPS adopts a zero-truncated Poisson regression framework to explicitly remove systematic biases in the PLAC-seq and HiChIP datasets, and then uses the normalized chromatin contact frequencies to identify significant chromatin interactions anchored at genomic regions bound by the protein of interest. MAPS shows superior performance over existing software tools in analysis of chromatin interactions centered on cohesin, CTCF and H3K4me3 associated regions in multiple cell types. MAPS is freely available at https://github.com/ijuric/MAPS.

bioinformatics↗

bioRxiv2018

A General Framework for Variable Selection in Linear Mixed Models with Applications to Genetic Studies with Structured Populations

Complex traits are known to be influenced by a combination of environmental factors and rare and common genetic variants. However, detection of such multivariate associations can be compromised by low statistical power and confounding by population structure. Linear mixed effects models (LMM) can account for correlations due to relatedness but have not been applicable in high-dimensional (HD) settings where the number of fixed effect predictors greatly exceeds the number of samples. False positives or false negatives can result from two-stage approaches, where the residuals estimated from a null model adjusted for the subjects relationship structure are sub-sequently used as the response in a standard penalized regression model. To overcome these challenges, we develop a general penalized LMM with a single random effect called ggmix for simultaneous SNP selection and adjustment for population structure in high dimensional prediction models. We develop a blockwise coordinate descent algorithm with automatic tuning parameter selection which is highly scalable, computationally efficient and has theoretical guarantees of convergence. Through simulations and three real data examples, we show that ggmix leads to more parsimonious models compared to the two-stage approach or principal component adjustment with better prediction accuracy. Our method performs well even in the presence of highly correlated markers, and when the causal SNPs are included in the kinship matrix. ggmix can be used to construct polygenic risk scores and select instrumental variables in Mendelian randomization studies. Our algorithms are available in an R package (https://github.com/greenwoodlab/ggmix). 1 Author SummaryThis work addresses a recurring challenge in the analysis and interpretation of genetic association studies: which genetic variants can best predict and are independently associated with a given phenotype in the presence of population structure ? Not controlling confounding due to geographic population structure, family and/or cryptic relatedness can lead to spurious associations. Much of the existing research has therefore focused on modeling the association between a phenotype and a single genetic variant in a linear mixed model with a random effect. However, this univariate approach may miss true associations due to the stringent significance thresholds required to reduce the number of false positives and also ignores the correlations between markers. We propose an alternative method for fitting high-dimensional multivariable models, which selects SNPs that are independently associated with the phenotype while also accounting for population structure. We provide an efficient implementation of our algorithm and show through simulation studies and real data examples that our method outperforms existing methods in terms of prediction accuracy and controlling the false discovery rate.

bioinformatics↗

bioRxiv2018

Wnt/Fgf crosstalk is required for the specification of tracheal basal progenitor cells

Basal progenitor cells are critical for the establishment and maintenance of the tracheal epithelium. However, it remains unclear how these progenitor cells are specified during foregut development. Here, we found that ablation of the Wnt chaperon protein Gpr177 (also known as Wntless) in the epithelium causes significant reduction in the numbers of basal progenitor cells accompanied by cartilage loss in Shh-Cre;Gpr177loxp/loxp mutants. Consistent with the association between cartilage and basal cell development, Nkx2.1+p63+ basal cells are co-present with cartilage nodules in Shh-Cre;Ctnnb1DM/loxp mutants which keep partial cell-cell adhesion but not the transcription regulation function of {beta}-catenin. More importantly, deletion of Ctnnb1 in the mesenchyme leads to the loss of basal cells and cartilage concomitant with the reduced transcript levels of Fgf10 in Dermo1-Cre;Ctnnb1loxp/loxp mutants. Furthermore, deletion of Fgf receptor 2 (Fgfr2) in the epithelium also leads to significantly reduced numbers of basal cells, supporting the importance of the Wnt/Fgf crosstalk in early tracheal development.

developmental biology↗

bioRxiv2018

Stable changing fluid shear stress promotes osteogenesis

ObjectiveBone marrow cells encounter various chemical and mechanical stimuli from the internal environment. In vivo, fluid shear stress (FSS) is one of the primary mechanical stimuli that affect bone marrow-derived mesenchymal stem cells (BMCs) activity. Since various cases of FSS influence BMCs activity differently, the purpose of this study is to determine how BMC activity in osteogenesis and osteoclastgenesis is affected by stable and unstable changing FSS.\n\nMethodBMCs samples from the femur of the mouse, divided in to three groups: stimulate by stable changing FSS, unstable changing FSS, and no FSS. RT-PCR would be applied to detect OPG, RANKL, ALP, OCN, RUNX2, and RANK of all the samples at the 3rd day. Alizarin red staining and TRAP staining would be applied to test all the samples at the 6th day.\n\nResultsThe S group samples showed the lowest level in RANKL mRNA and showed the highest level in OPG mRNA. RANKL/OPG mRNA in the S group was the smallest during three groups. Comparing with the C group samples, RUNX2 mRNA in the S group was increased significantly. RANK mRNA in the C group was three times more than S group. S group had the largest area of mineralized nodules, and largest number of area [≥]100{micro}m, [≥]500{micro}m2 or [≥]1000{micro}m2. The area of positive TRAP stain in S group was the smallest among three groups.\n\nConclusionStable changing FSS significantly increases osteogenesis relating to OPG-RANKL-RANK pathway. Compared with unstable changing FSS, stable changing FSS afford a more appropriate stimulation to osteogenesis.\n\nAbbreviations

cell biology↗

bioRxiv2018

Sequencing of the MHC region defines HLA-DQA1 as the major independent risk for anti-citrullinated protein antibodies (ACPA)-positive rheumatoid arthritis in Han population

The strong genetic contribution of the major histocompatibility complex (MHC) to rheumatoid arthritis (RA) susceptibility has been generally attributed to HLA-DRB1. However, due to the high linkage disequilibrium in the MHC region, it is difficult to define the real or/and additional independent genetic risks using the conventional HLA genotyping or chip-based microarray technology. By the capture sequencing of entire MHC region for discovery and HLA-typing for validation in 2,773 subjects of Han ancestry, we identified HLA-DQ1:160D as the strongest independent genetic risk for anti-citrullinated protein antibodies (ACPA)-positive RA in Han population (P = 6.16 x 10-36, OR=2.29). Further stepwise conditional analysis revealed that DR{beta}1:37N has an independent protective effect on ACPA-positive RA (P = 5.81 x 10-16, OR=0.49). The DQ1:160 coding allele DQA1*0303 displayed high impact on joint radiographic severity, especially in patients with early disease and smoking (P = 3.02 x 10-5). Interaction analysis by comparative molecular modeling revealed that the negative charge of DQ1:160D stabilizes the dimer of dimers, leading to an increased T cell activation. The electrostatic potential surface analysis indicated that the negative charged DR{beta}1:37N encoding alleles could bind with epitope P9 arginine, thus may result in a decreased RA susceptibility.\n\nIn this study, we provide the first evidence that HLA-DQA1, instead of HLA-DRB1, is the strongest and independent genetic risk for ACPA-positive RA in Chinese Han population. Our study also illustrates the value of MHC deep sequencing for fine mapping disease risk variants in the MHC region.

genetics↗