Genome wide association studies in diverse populations. Genomewide association studies in diverse populations ncbi nih. Although over 400 loci have been identified through genetic association studies, the genetic architecture of lipid levels is not fully characterized. Increasing diversity among study participants will advance our understanding of genetic architecture in all populations and ensure that genetic research is broadly applicable. Nucleotide diversity scans, 14 and association studies 5, 15 have been carried out in sorghum, but the resolution and sensitivity of these studies has been limited by the small number of. Genome wide association studies gwass are the method most often used by geneticists to interrogate the human genome, and they provide a costeffective way to identify the genetic variants underpinning complex traits and diseases. Metaanalysis of genome wide association studies of asthma in ethnically diverse north american populations.
Recently developed combinedphenotype methods which. Quantitative red blood cell rbc traits are highly polygenic clinically relevant traits, with approximately 500 reported gwas loci. Genomewide association studies in diverse populations. Genomewide association studies of asthma sciencedirect. 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. However, the need to expand the diversity of populations in gwas has. Genomewide association studies in ancestrally diverse populations. Most initial gwass have focused on genetically homogeneous cohorts from european populations given the limited availability of ethnic minority. Since the first genomewide association studies gwas publication a few. A standardized framework for representation of ancestry. In a population, contiguous stretches of founder chromosomes from the initial. Genomewide association studies reveal that diverse. Genome wide association studies gwas, which comprehensively assess genes related to multifactorial diseases and drug reactivity, have enhanced understanding of human diseases.
Genomewide association studies gwas of cancer have identified more than 700 risk loci, of which 80% of were first discovered in european ancestry populations, 15% in east asians, 3% in multiethnic scans, and less than 1% in african and latin american populations. Genomewide association gwa studies have identified a large number of singlenucleotide polymorphisms snps associated with disease phenotypes. In this study, five ear traits kernel length and width, ear length and diameter, cob. Box 1 populations in past genomewide association studies to assess the extent to which noneuropean populations have been incorporated into genome wide association gwa studies, we examined the distribution of study populations across 492 gwa articles in the national human genome research institute nhgri catalogue of gwa results6. Genomewide association studies in africans and african. Genomics of disease risk in globally diverse populations gwern. The plant genome abstract original research genomewide. Genomewide association studies reveal the genetic basis. In addition, genome wide association studies gwas have been used to elucidate the genetic. This european bias has important implications for risk prediction of diseases across global populations. Genomewide association studies in ancestrally diverse. Genomewide association gwa studies have identified a large number of snps associated with disease phenotypes.
Benefits and limitations of genomewide association studies. The article describes the limited population diversity of genome wide association studies and its resulting impact on the development of commercial genetic tests. A metaanalysis of genomewide association studies for. Author summary blood lipid levels are closely linked to cardiometabolic diseases, and genetic factors play an important role in their metabolism and regulation. Genome wide association studies gwass have focused primarily on populations of european descent, but it is essential that diverse populations become better represented. A genome wide association study gwas combining highdensity markers with a diverse germplasm collection provides higher mapping resolution than conventional qtl mapping based on biparent derived segregating populations and enables the prediction or identi. The lack of representation of diverse populations in previous studies resulted in a. In genetics, a genome wide association study gwa study, or gwas, also known as whole genome association study wga study, or wgas, is an observational study of a genome wide set of genetic variants in different individuals to see if any variant is associated with a trait. Introduction the science of genomewide association studies gwas emerged about a decade ago as a powerful scientific tool to identify genes associated with the outward traits of an organism. Metaanalysis of genome wide association studies of asthma in ethnically diverse north american populations article pdf available in nature genetics 439. Genetic architecture and evolution of complex traits and. Genome wide association study gwas is a powerful tool for unraveling the molecular basis for phenotypic diversity.
Impact of limited population diversity of genomewide association. James holland and colleagues report a genome wide association study for resistance to southern leaf blight slb in the maize nested association mapping population. Impact of limited population diversity of genomewide. Genome wide association studies gwas have evolved over the last ten years into a powerful tool for investigating the genetic architecture of human disease.
Minoritycentric metaanalyses of blood lipid levels. Genomic studies of african populations or isolated populations may identify rare variants because of differences in linkage disequilibirum size. Genetic analyses of diverse populations improves discovery for. Investigation of these traits would help to develop highyield varieties in maize. A metaanalysis of genomewide association studies for serum total ige in diverse study populations. In addition, genome wide association studies gwas have been used to elucidate the genetic basis of agronomic traits in rice 12 and maize 10. Genome wide association study gwas using diverse populations provides another strategy to effectively fine map qtl due to a large number of historical recombination events that lead to the rapid decay of linkage disequilibrium ld flintgarcia et al. A recent genome wide association study modeling the effect of genotypebysex interaction on obesity phenotypes demonstrated sexinfluenced associations between genetic variation at the lyplal1 locus and obesityrelated traits. In addition, genome wide association studies gwas have been used to elucidate the genetic basis of agronomic traits in rice and maize. In this commentary, we justify the need to study more diverse populations using both empirical examples and theoretical reasoning. Genomewide association studies gwas have laid the foundation for investigations into the biology of complex traits, drug development and. Genomewide association studies caitlin collins, thibaut jombart imperial college london mrc centre for outbreak analysis and modelling august 6, 2015 abstract this practical provides an introduction to genomewide association studies gwas in r.
Genetic diversity and genomewide association study of. The majority of studies of genetic association with disease have been performed in europeans. Genome wide association gwa studies have identified a large number of singlenucleotide polymorphisms snps associated with disease phenotypes. Review transethnic genome wide association studies. This has led to the construction of polygenic predictors of complex traits for potential clinical applications and to their use in studies of polygenic. Genomewide association study of quantitative resistance. Gwas of cancer in noneuropean ancestry populations.
Dan nicolae, carole ober and colleagues report a metaanalysis of genome wide association studies for asthma in a collection of ethnically diverse north american populations. This study suggests that fto may be a gene playing a role in the commonly observed sexdimorphism in adiposity. Concepts and relevance of genomewide association studies. Genome wide association studies gwas of cancer have identified more than 700 risk loci, of which 80% of were first discovered in european ancestry populations, 15% in east asians, 3% in multiethnic scans, and less than 1% in african and latin american populations.
Genomewide association studies of cancer in diverse populations. Pdf metaanalysis of genomewide association studies of. Genome wide association studies of hiv1 host control in ethnically diverse chinese populations article pdf available in scientific reports 5. Genomewide association studies gwass have focused primarily on populations of european descent, but it is essential that diverse populations become better represented. Alterations of the dna of a genome that results in the cell having an abnormal or, for certain genes, a normal variation in the. This association mapping strategy was firstly applied in plants in the beginning of the 21st century as a candidate gene association. Genome wide association study gwas uses the linkage disequilibrium ld in the whole genome to determine the genes affecting certain phenotype. Transethnic genomewide association studies cyberleninka. Used to infer population history and study diversity. Genomewide association studies of cancer in diverse. Genome wide association studies in practice risch and merikangas 1996 says that to detect a disease allele with a.
Most genome wide association gwa studies have been performed in populations of european descent. Advantages and challenges of mapping in diverse populations article pdf available in genome medicine 610. From 2007, gwas of susceptibility to asthma in caucasian, mexican, and africanancestry populations have been conducted and several susceptible loci were identified. Here, we first discuss crop genome studies and describe the development of sequencingbased genotyping and genomewide association studies in crops. Pdf genomewide association studies gwas have evolved over the last ten. Genome wide association studies of cancer in diverse populations sungshim l. Natural variations and genomewide association studies in. Genome wide association studies gwas have been able to associate large regions of the genome to specific traits and diseases, explaining a fraction of their observed phenotypic variation. Genome wide snp scans of population genetic parameters have been used in domesticated species to identify loci under selection jiao et al. We performed a metaanalysis of north american genome wide association studies gwas of asthma in 5,416 asthma cases representing european americans, african americansafrican caribbeans, and latinos, and replicated five regions among the most significant signals in 12,649 individuals from the same ethnic groups. Metaanalysis of genomewide association studies of asthma in ethnically diverse north american populations. The majority of rbc trait gwas have been performed in european or east asianancestry populations, despite evidence that rare or ancestryspecific variation contributes substantially to rbc trait heritability. Metaanalysis of genomewide association studies of asthma. Replication of 6 obesity genes in a metaanalysis of.
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