Introduction to Risk Loci

Two genome-wide association studies have reported a few potential dystonia risk loci; but conclusions have been limited by small sample sizes, partial coverage of genetic variants, or poor reproducibility.

BACKGROUND Genome-wide association studies (GWAS) have not identified replicable genetic risk loci for stress or urgency urinary incontinence.

In addition to already established risk loci, our data identify and replicate two genome-wide significant loci at 17q21.

We identified four genome-wide significant risk loci for EOS in the combined samples (2,159 EOS cases and 6,561 controls), including 1p36.

Transcriptome-wide association studies [TWAS] associate gene expression with genetic susceptibility to disease, providing functional insight into risk loci.

Of the nine genes with statistically independent transcriptome-wide association signals, seven are located in known Alzheimer’s disease risk loci: BIN1, PTK2B, SPI1, MS4A4A, MS4A6E, APOE and PVR.

Late-onset AD is highly heritable (60 to 80%), and over 40 risk loci for AD have been identified via large genome-wide association studies, most of which are common variants with small effect sizes.

Our understanding of the pathogenesis of these diseases has greatly benefited from an expansion of population genetic studies from pioneering familial studies to large genome-wide association studies; we now have multiple risk loci for each venous disease.

We map molecular quantitative trait loci and find several potential ALS risk loci that may act through gene expression or splicing in the spinal cord and assign putative cell-types for FNBP1, ACSL5, SH3RF1 and NFASC.

We performed cis‐expression quantitative trait loci (eQTL) mapping for 376 lung cancer related GWAS loci in 227 TCGA lung adenocarcinoma (LUAD) and reported two risk loci as eQTL of miRNA.

Herein, we performed phenome-wide association study (PheWAS), tissue and immune-cell specific expression/splicing quantitative trait loci (eQTL/sQTL), and colocalization analyses for genetic risk loci suggestively associated with severe COVID-19 with respiratory failure.

Herein, we performed phenome-wide association study, tissue and immune-cell-specific expression quantitative trait locus (eQTL)/splicing quantitative trait locus, and colocalization analyses for genetic risk loci suggestively associated with severe COVID-19 with respiratory failure.

More than 240 genetic risk loci have been associated with inflammatory bowel disease (IBD), but little is known about how they contribute to disease development in involved tissue.

To examine the relation between ALS and 10 autoimmune diseases, including asthma, celiac disease (CeD), Crohn’s disease (CD), inflammatory bowel disease (IBD), multiple sclerosis (MS), psoriasis, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type 1 diabetes (T1D), and ulcerative colitis (UC), and identify shared risk loci, we first estimated the genetic correlation using summary statistics from genome-wide association studies, and then analyzed the genetic enrichment leveraging the conditional false discovery rate statistical method.

Interpretation of the function of non-coding risk loci for neuropsychiatric disorders and brain-relevant traits via gene expression and alternative splicing quantitative trait locus (e/sQTL) analyses is generally performed in bulk post-mortem adult tissue.

Expression quantitative trait loci (eQTL) studies are used to understand the regulatory function of non-coding genome-wide association study (GWAS) risk loci, but colocalization alone does not demonstrate a causal relationship of gene expression affecting a trait.

Cross-disorder meta-analysis of OA and MD identified 56 genomic risk loci (Pmeta ≤ 5 × 10–8), which show heightened expression of the associated genes in the brain and pituitary.

Subsequent conjunctional false discovery rate analysis identified 44 and 23 schizophrenia risk loci shared with total SA and average TH, respectively.

Identifying novel risk factors, including genetic risk loci, could be instrumental in risk stratification and implementation of prevention strategies.

BACKGROUND Genome-wide association studies (GWAS) have not identified replicable genetic risk loci for stress or urgency urinary incontinence.

It is largely heritable, and genetic screening has identified single‐nucleotide polymorphisms (SNPs) marking genomic risk loci.

In meta-analyses of GAD (N=489,579) and PTSD (N=497,803), we discovered many novel genomic risk loci (13 for GAD and 40 for PTSD).

Background: Prior genome-wide association studies have identified numerous lung cancer risk loci and reveal substantial etiologic heterogeneity across histologic subtypes.

A combination of genetic and functional approaches has identified three independent breast cancer risk loci at 2q35.

Results: We identified two independent risk loci harboring genome-wide significant variants (P < 5 x 10-8, OR [≥] 2.

Results After linkage disequilibrium expansion of the previously reported tag associated SNPs, we identified 192 genetic variants at 8 independent risk loci.

By integrating GO-CaRT maps with genome-wide association study data, we found speckle-associated domains to be enriched for schizophrenia risk loci, indicating a physical relationship between these disease-associated genetic variants and a specific nuclear structure.

Subsequent conjunctional false discovery rate analysis identified 44 and 23 schizophrenia risk loci shared with total SA and average TH, respectively.

BACKGROUND & AIMS Genome-wide association studies (GWAS) have identified several risk loci for gallstone disease.

Objective: Genome-wide association studies (GWAS) have identified several risk loci for gallstone disease.

Genome-wide association studies (GWAS) have identified 113 single nucleotide polymorphisms (SNPs) affecting the risk of developing ankylosing spondylitis (AS), and an on-going GWAS study will likely identify 100+ new risk loci.

We believe that, by integrating the largest ALS GWAS summary statistic with gene expression to identify new risk loci and causal genes, our study provides strong candidates for molecular basis experiments in ALS.

Background Genome-wide association studies of prostate cancer have identified >250 significant risk loci, but the causal variants and mechanisms for these loci remain largely unknown.

We identified four genome-wide significant risk loci for EOS in the combined samples (2,159 EOS cases and 6,561 controls), including 1p36.

We investigated if MS risk loci might mediate the gender imbalance in MS.

We identified differentially expressed host miRNAs in EBV infected B cells (LCLs) and putative host/EBV miRNA interactions with MS risk loci.

Description Single-cell ATAC sequencing maps the cell type–specific regulatory potential of transcription factors and autoimmune disease risk loci.

Of the nine genes with statistically independent transcriptome-wide association signals, seven are located in known Alzheimer’s disease risk loci: BIN1, PTK2B, SPI1, MS4A4A, MS4A6E, APOE and PVR.

CONCLUSIONS These results together suggest that rs4420550 is a functional risk variation, and this study illustrates an example of comprehensive functional characterization of schizophrenia GWAS risk loci.

Of these, 96 resided within previously identified GWAS risk loci and 18 were novel (CAND1, EGFLAM, EZR, FAM114A1, FOCAD, GAS8, HOMER3, KPTN, MGP, NLRC4, RGS19, SDCCAG3, STX4, TSPAN11, TXNRD3, UFL1, WASF1, and WWP2).

In addition to identifying novel risk loci for PD, these results demonstrate that WGS-based imputation and analysis of existing exome genotype data can identify novel intronic and intergenic SNP effects associated with complex disease risk.

A bivariate meta-analysis identified 28 loci associated with endometriosis and EOC, including two novel risk loci, and 19 with evidence for a single underlying causal variant.

In addition to already established risk loci, our data identify and replicate two genome-wide significant loci at 17q21.

Recently, several GWAS performed in other ethnic groups have shown the importance of replicating studies that identify previously established risk loci and searching for novel risk loci.

Regional associations were replicated with known risk loci for atherosclerosis and CVDs with different lead SNPs than in Europeans and significant enrichment for oestrogen response genes for female-specific signals were identified.

Conclusion: We confirmed two known risk loci for HNC while concurrently identifying an additional four novel variants involved in the immune pathway genes that may contribute to HNC susceptibility.

To examine whether genetic enrichment exists between ALS and obesity-related traits and to identify shared risk loci, we analyzed summary statistics from genome-wide association studies using the conditional false discovery rate statistical framework, and further conducted functional enrichment analysis.

Using genome-wide association study (GWAS) data, we explored the relationships between these non-cancerous gynecological diseases and endometrial cancer risk by assessing genetic correlation, causal relationships and shared risk loci.

Genome-wide association studies (GWASs) have identified risk loci for complex traits and diseases that are disproportionately located at the non-coding regions of the genome.

Although recent genome‐wide association studies have identified risk loci that strongly associates with autism spectrum disorder (ASD), how to pinpoint the causal genes remains a challenge.

Our understanding of the pathogenesis of these diseases has greatly benefited from an expansion of population genetic studies from pioneering familial studies to large genome-wide association studies; we now have multiple risk loci for each venous disease.

Cross-disorder meta-analysis reveals multiple risk loci that appear pleiotropic across MG and correlated disorders.

RESULTS: Two risk loci were detected: the well-known functional variant rs1229984 in ADH1B and rs3782886 in BRAP (near the ALDH2 gene locus) are the lead variants.

We performed cis‐expression quantitative trait loci (eQTL) mapping for 376 lung cancer related GWAS loci in 227 TCGA lung adenocarcinoma (LUAD) and reported two risk loci as eQTL of miRNA.

This study generated a high-resolution contact map from epithelial ovarian cancer (EOC) cells with two H3K27ac-HiChIP libraries and analyzed the underlying gene networks for 15 risk loci identified from the largest EOC GWAS.

We conducted a cross-ancestry GWAS in ALS including 29,612 ALS patients and 122,656 controls which identified 15 risk loci in ALS.

We therefore sought to simultaneously identify functional genetic variants and assess retinoid pathway regulation of MDD risk loci.

We therefore sought to simultaneously identify functional genetic variants and assess retinoid pathway regulation of MDD risk loci.

Although over 120 risk loci have been identified for glaucoma, a large portion of its heritability is still unexplained.

Research has successfully identified more than 120 risk loci, defined mainly by haplotypes (a set of variants that are coinherited), that are associated with increased SLE susceptibility.

This suggests that our findings are specific to FTD and are likely to be biologically relevant highlights of genes at different FTD risk loci that are contributing to the disease pathology.

The majority of FTD cannot be genetically explained yet and it is likely that there are still FTD risk loci to be discovered.

Hundreds of autoimmune risk loci have been discovered in coding and non-coding regions of the genome; however, their function and the causal alleles functioning within these loci have been difficult to discern.

Most autoimmunity-inducing NLRs are encoded within highly variable NLR gene clusters with no known immune functions, which were termed autoimmune risk loci.

At 28 of the 52 risk loci, CWAS identified regulatory mechanisms that are not observable via eQTLs, implicating genes with complex or context-specific regulation that are overlooked by current approaches that relying on steady-state transcript measurements.

At 28 of the 52 risk loci, CWAS identified regulatory mechanisms that are not observable via eQTLs, implicating genes with complex or context-specific regulation that are overlooked by current approaches that relying on steady-state transcript measurements.

Background: Several genetic susceptibility risk loci for ischemic stroke have been identified.

Several low penetration susceptibility risk loci or genes (i.

Previous genome-wide association studies (GWAS) of hematological traits have identified over 10,000 distinct trait-specific risk loci, but the underlying causal mechanisms at these loci remain incompletely characterized.

Design To identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48 214 CRC cases and 64 159 controls of European ancestry.

Specifically expressed genes in iDANs, as well as those from isogenic induced GABAergic and glutamatergic neurons, were enriched in loci conferring heritability for cannabis use disorder, schizophrenia, and bipolar disorder; however, each neuronal subtype demonstrated subtype-specific heritability enrichments in biologically relevant pathways, and iDANs alone were uniquely enriched in autism spectrum disorder risk loci.

By integrating cell-type-specific chromatin accessibility-QTL and brain-relevant genome-wide association data, we were able to fine-map and identify regulatory mechanisms underlying noncoding neuropsychiatric disorder risk loci.

To identify risk loci, we conduct a large multi-ethnic meta-analysis of genome-wide association studies on a total of 34,179 cases and 349,321 controls, identifying 44 previously unreported risk loci and confirming 83 loci that were previously known.

In the present study, we used combined whole-exome sequencing and linkage analysis to identify risk loci and dissect the contribution of common and rare variants in families with a high density of illness.

Several Genome-Wide Association Studies (GWASs) have revealed more than 100 risk loci for RA.

Background Genome-wide association studies have reported more than 100 risk loci for rheumatoid arthritis (RA).

This study generated a high-resolution contact map from epithelial ovarian cancer (EOC) cells with two H3K27ac-HiChIP libraries and analyzed the underlying gene networks for 15 risk loci identified from the largest EOC GWAS.

AIS is known to have a significant genetic component, and despite a handful of risk loci identified in unrelated individuals by GWAS and next-generation sequencing methods, the underlying etiology of the condition remains largely unknown.

In conclusion, our results are consistent with the hypothesis that genetic risk loci associated with multiple AiDs converge on a core set of biological processes that potentially contribute to the emergence of polyautoimmunity.

Both consistent and temporal-predominant edQTLs co-localize with risk loci associated with neurological traits and disorders, including attention deficit hyperactivity disorder, schizophrenia, and sleep disorders.

Candidate genetic risk loci shared by obesity and alcohol use disorders have been identified in molecules classically associated with both metabolic and motivational functions.

Subsequent conjunctional false discovery rate analysis identified 44 and 23 schizophrenia risk loci shared with total SA and average TH, respectively.

Herein, we performed phenome-wide association study (PheWAS), tissue and immune-cell specific expression/splicing quantitative trait loci (eQTL/sQTL), and colocalization analyses for genetic risk loci suggestively associated with severe COVID-19 with respiratory failure.

Herein, we performed phenome-wide association study, tissue and immune-cell-specific expression quantitative trait locus (eQTL)/splicing quantitative trait locus, and colocalization analyses for genetic risk loci suggestively associated with severe COVID-19 with respiratory failure.

Results: We identified two independent risk loci harboring genome-wide significant variants (P < 5 x 10-8, OR [≥] 2.

Results We identified 2 independent risk loci harboring genome-wide significant variants (p < 5 × 10−8, OR ≥ 2.

Recent large genome-wide association studies have identified multiple confident risk loci linked to addiction-associated behavioral traits.

The genomewide study results are suggestive of modifying effects of genetic risk loci linked to PD, on the neurological phenotype of FMR1-CGG small expansion carriers, resulting in an oligosymptomatic kinetic tremor seen in FXTAS spectrum, but also consistent with essential tremor.