Editorial: Genome-wide association studies of COVID-19 among diverse human populations.
Ontology highlight
ABSTRACT:
SUBMITTER: Cheng ZS
PROVIDER: S-EPMC9753975 | biostudies-literature | 2022
REPOSITORIES: biostudies-literature
Publications
Editorial: Genome-wide association studies of COVID-19 among diverse human populations.
Frontiers in genetics 20221201
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Project description:Genome-wide association studies (GWAS) of cancer have identified more than 700 risk loci, of which approximately 80% were first discovered in European ancestry populations, approximately 15% in East Asians, 3% in multiethnic scans, and less than 1% in African and Latin American populations. These percentages closely mirror the distribution of samples included in the discovery phase of cancer GWAS to date (84% European, 11% East Asian, 4% African, and 1% Latin American ancestry). GWAS in non-European ancestry populations have provided insight into ancestry-specific variation in cancer and have pointed to regions of susceptibility that are of particular importance in certain populations. Uncovering and characterizing cancer risk loci in diverse populations is critical for understanding underlying biological mechanisms and developing future genetic risk prediction models in non-European ancestry populations. New GWAS and continued collaborations will be required to eliminate population inequalities in the number of studies, sample sizes, and variant content on GWAS arrays, and to better align genetic research in cancer to the global distribution of race/ethnicity Cancer Epidemiol Biomarkers Prev; 27(4); 405-17. ©2018 AACRSee all articles in this CEBP Focus section, "Genome-Wide Association Studies in Cancer."
| S-EPMC5740019 | biostudies-literature
Project description:Genome-wide association studies (GWASs) have focused primarily on populations of European descent, but it is essential that diverse populations become better represented. Increasing diversity among study participants will advance our understanding of genetic architecture in all populations and ensure that genetic research is broadly applicable. To facilitate and promote research in multi-ancestry and admixed cohorts, we outline key methodological considerations and highlight opportunities, challenges, solutions, and areas in need of development. Despite the perception that analyzing genetic data from diverse populations is difficult, it is scientifically and ethically imperative, and there is an expanding analytical toolbox to do it well.
| S-EPMC6939869 | biostudies-literature
Project description:Genome-wide association studies (GWAS) have become the preferred experimental design in exploring the genetic etiology of complex human traits and diseases. Standard SNP-based meta-analytic approaches have been utilized to integrate the results from multiple experiments. This fundamentally assumes that the patterns of linkage disequilibrium (LD) between the underlying causal variants and the directly genotyped SNPs are similar across the populations for the same SNPs to emerge with surrogate evidence of disease association. We introduce a novel strategy for assessing regional evidence of phenotypic association that explicitly incorporates the extent of LD in the region. This provides a natural framework for combining evidence from multi-ethnic studies of both dichotomous and quantitative traits that (i) accommodates different patterns of LD, (ii) integrates different genotyping platforms and (iii) allows for the presence of allelic heterogeneity between the populations. Our method can also be generalized to perform gene-based or pathway-based analyses. Applying this method on real GWAS data in type 2 diabetes (T2D) boosted the association evidence in regions well-established for T2D etiology in three diverse South-East Asian populations, as well as identified two novel gene regions and a biologically convincing pathway that are subsequently validated with data from the Wellcome Trust Case Control Consortium.
| S-EPMC3306862 | biostudies-other
Project description:Genome-wide association studies (GWASs) have revealed several genetic loci associated with HIV-1 outcome following infection (e.g., HLA-C at 6p21.33) in multi-ethnic populations with genetic heterogeneity and racial/ethnic differences among Caucasians, African-Americans, and Hispanics. To systematically investigate the inherited predisposition to modulate HIV-1 infection in Chinese populations, we performed GWASs in three ethnically diverse HIV-infected patients groups (i.e., HAN, YUN, and XIN, N = 538). The reported loci at 6p21.33 was validated in HAN (e.g., rs9264942, P = 0.0018). An independent association signal (rs2442719, P = 7.85 × 10(-7), HAN group) in the same region was observed. Imputation results suggest that haplotype HLA-B*13:02/C*06:02, which can partially account for the GWAS signal, is associated with lower viral load in Han Chinese. Moreover, several novel loci were identified using GWAS approach including the top association signals at 6q13 (KCNQ5, rs947612, P = 2.15 × 10(-6)), 6p24.1 (PHACTR1, rs202072, P = 3.8 × 10(-6)), and 11q12.3 (SCGB1D4, rs11231017, P = 7.39 × 10(-7)) in HAN, YUN, and XIN groups, respectively. Our findings imply shared or specific mechanisms for host control of HIV-1 in ethnically diverse Chinese populations, which may shed new light on individualized HIV/AIDS therapy in China.
| S-EPMC4454153 | biostudies-literature
Project description:Genome-wide association studies (GWASs) are a research approach used to identify genetic variants associated with common diseases, like COVID-19. The lead genetic variants (n = 41) reported by the eleven largest COVID-19 GWASs are mapped to 22 different chromosomal regions. The loci 3q21.31 (LZTFL1 and chemokine receptor genes) and 9q34.2 (ABO), associated with disease severity and susceptibility to infection, respectively, were the most replicated findings across studies. Genes involved with mucociliary clearance (CEP97, FOXP4), viral-entry (ACE2, SLC6A20) and mucosal immunity (MIR6891) are associated with the risk of SARS-CoV-2 infection while genes of antiviral immune response (IFNAR2, OAS1), leukocyte trafficking (CCR9, CXCR6) and lung injury (DPP9, NOTCH4) are associated with severe disease. The biological processes underlying the risk of infection occur prominently, but not exclusively, in the upper airways whereas the severe COVID-19-associated processes in alveolar-capillary interface. The COVID-19 GWASs has unraveled key genetic mechanisms of SARS-CoV-2 pathogenesis, although the genetic basis of other COVID-19 related phenotypes (long COVID and neurological impairment) remains to be elucidated.
| S-EPMC9584840 | biostudies-literature
Project description:Asthma is a common disease with a complex risk architecture including both genetic and environmental factors. We performed a meta-analysis of North American genome-wide association studies of asthma in 5,416 individuals with asthma (cases) including individuals of European American, African American or African Caribbean, and Latino ancestry, with replication in an additional 12,649 individuals from the same ethnic groups. We identified five susceptibility loci. Four were at previously reported loci on 17q21, near IL1RL1, TSLP and IL33, but we report for the first time, to our knowledge, that these loci are associated with asthma risk in three ethnic groups. In addition, we identified a new asthma susceptibility locus at PYHIN1, with the association being specific to individuals of African descent (P = 3.9 × 10(-9)). These results suggest that some asthma susceptibility loci are robust to differences in ancestry when sufficiently large samples sizes are investigated, and that ancestry-specific associations also contribute to the complex genetic architecture of asthma.
| S-EPMC3445408 | biostudies-literature
Project description:BackgroundIgE is both a marker and mediator of allergic inflammation. Despite reported differences in serum total IgE levels by race-ethnicity, African American and Latino subjects have not been well represented in genetic studies of total IgE.ObjectiveWe sought to identify the genetic predictors of serum total IgE levels.MethodsWe used genome-wide association data from 4292 subjects (2469 African Americans, 1564 European Americans, and 259 Latinos) in the EVE Asthma Genetics Consortium. Tests for association were performed within each cohort by race-ethnic group (ie, African American, Latino, and European American) and asthma status. The resulting P values were meta-analyzed, accounting for sample size and direction of effect. Top single nucleotide polymorphism associations from the meta-analysis were reassessed in 6 additional cohorts comprising 5767 subjects.ResultsWe identified 10 unique regions in which the combined association statistic was associated with total serum IgE levels (P<5.0×10(-6)) and the minor allele frequency was 5% or greater in 2 or more population groups. Variant rs9469220, corresponding to HLA-DQB1, was the single nucleotide polymorphism most significantly associated with serum total IgE levels when assessed in both the replication cohorts and the discovery and replication sets combined (P=.007 and 2.45×10(-7), respectively). In addition, findings from earlier genome-wide association studies were also validated in the current meta-analysis.ConclusionThis meta-analysis independently identified a variant near HLA-DQB1 as a predictor of total serum IgE levels in multiple race-ethnic groups. This study also extends and confirms the findings of earlier genome-wide association analyses in African American and Latino subjects.
| S-EPMC3596497 | biostudies-literature
Project description:Genome-wide association studies (GWAS) may be biased by population stratification (PS). We conducted empirical quantification of the magnitude of PS among human populations and its impact on GWAS. Liver tissues were collected from 979, 59 and 49 Caucasian Americans (CA), African Americans (AA) and Hispanic Americans (HA), respectively, and genotyped using Illumina650Y (Ilmn650Y) arrays. RNA was also isolated and hybridized to Agilent whole-genome gene expression arrays. We propose a new method (i.e., hgdp-eigen) for detecting PS by projecting genotype vectors for each sample to the eigenvector space defined by the Human Genetic Diversity Panel (HGDP). Further, we conducted GWAS to map expression quantitative trait loci (eQTL) for the approximately 40,000 liver gene expression traits monitored by the Agilent arrays. HGDP-eigen performed similarly to the conventional self-eigen methods in capturing PS. However, leveraging the HGDP offered a significant advantage in revealing the origins, directions and magnitude of PS. Adjusting for eigenvectors had minor impacts on eQTL detection rates in CA. In contrast, for AA and HA, adjustment dramatically reduced association findings. At an FDR = 10%, we identified 65 eQTLs in AA with the unadjusted analysis, but only 18 eQTLs after the eigenvector adjustment. Strikingly, 55 out of the 65 unadjusted AA eQTLs were validated in CA, indicating that the adjustment procedure significantly reduced GWAS power. A number of the 55 AA eQTLs validated in CA overlapped with published disease associated SNPs. For example, rs646776 and rs10903129 have previously been associated with lipid levels and coronary heart disease risk, however, the rs10903129 eQTL was missed in the eigenvector adjusted analysis.
| S-EPMC2805717 | biostudies-literature
Project description:BackgroundDental caries is one of the most common chronic diseases and is influenced by a complex interplay of genetic and environmental factors. Most previous genetic studies of caries have focused on identifying genes that contribute to dental caries in specific ethnic groups, usually of European descent.MethodsThe aim of this study is to conduct a genome-wide association study (GWAS) to identify associations affecting susceptibility to caries in a large multiethnic population from Argentina, the Philippines, Guatemala, Hungary, and the USA, originally recruited for studies of orofacial clefts (POFC, N = 3686). Ages of the participants ranged from 2 to 12 years for analysis of the primary dentition, and 18-60 years for analysis of the permanent dentition. For each participant, dental caries was assessed by counts of decayed and filled teeth (dft/DFT) and genetic variants (single nucleotide polymorphisms, SNPs) were genotyped or imputed across the entire genome. Caries was analyzed separately for the primary and permanent dentitions, with age, gender, and presence/absence of any type of OFC treated as covariates. Efficient Mixed-Model Association eXpedited (EMMAX) was used to test genetic association, while simultaneously accounting for relatedness and stratification.ResultsWe identified several suggestive loci (5 × 10-8 < P < 5 × 10-6) within or near genes with plausible biological roles for dental caries, including a cluster of taste receptor genes (TAS2R38, TAS2R3, TAS2R4, TASR25) on chromosome 7 for the permanent dentition analysis, and DLX3 and DLX4 on chromosome 17 for the primary dentition analysis. Genome-wide significant results were seen with SNPs in the primary dentition only; however, none of the identified genes near these variants have known roles in cariogenesis.ConclusionThe results of this study warrant further investigation and may lead to a better understanding of cariogenesis in diverse populations, and help to improve dental caries prediction, prevention, and/or treatment in future.
| S-EPMC8311973 | biostudies-literature
Project description:BACKGROUND:Genome-wide association studies have found type 2 diabetes-associated variants in the HNF1B gene to exhibit reciprocal associations with prostate cancer risk. We aimed to identify whether these variants may have an effect on cancer risk in general versus a specific effect on prostate cancer only. METHODOLOGY/PRINCIPAL FINDINGS:In a collaborative analysis, we collected data from GWAS of cancer phenotypes for the frequently reported variants of HNF1B, rs4430796 and rs7501939, which are in linkage disequilibrium (r(2) = 0.76, HapMap CEU). Overall, the analysis included 16 datasets on rs4430796 with 19,640 cancer cases and 21,929 controls; and 21 datasets on rs7501939 with 26,923 cases and 49,085 controls. Malignancies other than prostate cancer included colorectal, breast, lung and pancreatic cancers, and melanoma. Meta-analysis showed large between-dataset heterogeneity that was driven by different effects in prostate cancer and other cancers. The per-T2D-risk-allele odds ratios (95% confidence intervals) for rs4430796 were 0.79 (0.76, 0.83)] per G allele for prostate cancer (p<10(-15) for both); and 1.03 (0.99, 1.07) for all other cancers. Similarly for rs7501939 the per-T2D-risk-allele odds ratios (95% confidence intervals) were 0.80 (0.77, 0.83) per T allele for prostate cancer (p<10(-15) for both); and 1.00 (0.97, 1.04) for all other cancers. No malignancy other than prostate cancer had a nominally statistically significant association. CONCLUSIONS/SIGNIFICANCE:The examined HNF1B variants have a highly specific effect on prostate cancer risk with no apparent association with any of the other studied cancer types.
| S-EPMC2878330 | biostudies-literature