scholarly journals Ancestry-informative markers for African Americans based on the Affymetrix Pan-African genotyping array

2014 ◽  
Author(s):  
Xu Zhang ◽  
Wenbo Mu ◽  
Cong Liu ◽  
Wei Zhang
Keyword(s):  
African Americans ◽  
Complex Traits ◽  
Association Studies ◽  
African Ancestry ◽  
Genetic Admixture ◽  
Admixture Mapping ◽  
Genome Wide Association Studies ◽  
Ancestry Informative Markers ◽  
Pan African ◽  
Genome Wide

Genetic admixture has been utilized as a tool for identifying loci associated with complex traits and diseases in recently admixed populations such as African Americans. In particular, admixture mapping is an efficient approach to identifying genetic basis for those complex diseases with substantial racial or ethnic disparities. Though current advances in admixture mapping algorithms may utilize the entire panel of SNPs, providing ancestry-informative markers (AIMs) that can differentiate parental populations and estimate ancestry proportions in an admixed population may particularly benefit admixture mapping in studies of limited samples, help identify unsuitable individuals (e.g., through genotyping the most informative ancestry markers) before starting large genome-wide association studies (GWAS), or guide larger scale targeted deep re-sequencing for determining specific disease-causing variants. Defining panels of AIMs based on commercial, high-throughput genotyping platforms will facilitate the utilization of these platforms for simultaneous admixture mapping of complex traits and diseases, in addition to conventional GWAS. Here, we describe AIMs detected based on the Shannon Information Content (SIC) or Fst for African Americans with genome-wide coverage that were selected from ~2.3 million single nucleotide polymorphisms (SNPs) covered by the Affymetrix Axiom Pan-African array, a newly developed genotyping platform optimized for individuals of African ancestry.

scholarly journals Ancestry-informative markers for African Americans based on the Affymetrix Pan-African genotyping array

2014 ◽  
Author(s):  
Xu Zhang ◽  
Wenbo Mu ◽  
Cong Liu ◽  
Wei Zhang
Keyword(s):  
African Americans ◽  
Complex Traits ◽  
Association Studies ◽  
African Ancestry ◽  
Genetic Admixture ◽  
Admixture Mapping ◽  
Genome Wide Association Studies ◽  
Ancestry Informative Markers ◽  
Pan African ◽  
Genome Wide

Genetic admixture has been utilized as a tool for identifying loci associated with complex traits and diseases in recently admixed populations such as African Americans. In particular, admixture mapping is an efficient approach to identifying genetic basis for those complex diseases with substantial racial or ethnic disparities. Though current advances in admixture mapping algorithms may utilize the entire panel of SNPs, providing ancestry-informative markers (AIMs) that can differentiate parental populations and estimate ancestry proportions in an admixed population may particularly benefit admixture mapping in studies of limited samples, help identify unsuitable individuals (e.g., through genotyping the most informative ancestry markers) before starting large genome-wide association studies (GWAS), or guide larger scale targeted deep re-sequencing for determining specific disease-causing variants. Defining panels of AIMs based on commercial, high-throughput genotyping platforms will facilitate the utilization of these platforms for simultaneous admixture mapping of complex traits and diseases, in addition to conventional GWAS. Here, we describe AIMs detected based on the Shannon Information Content (SIC) or Fst for African Americans with genome-wide coverage that were selected from ~2.3 million single nucleotide polymorphisms (SNPs) covered by the Affymetrix Axiom Pan-African array, a newly developed genotyping platform optimized for individuals of African ancestry.

scholarly journals Transcriptome association studies of neuropsychiatric traits in African Americans implicate PRMT7 in schizophrenia

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7778 ◽  
Author(s):  
Peter N. Fiorica ◽  
Heather E. Wheeler
Keyword(s):  
Bipolar Disorder ◽  
African Americans ◽  
Complex Traits ◽  
Multiple Testing ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Potential Candidate ◽  
Candidate Locus ◽  
Genome Wide ◽  
Multiple Testing Adjustment

In the past 15 years, genome-wide association studies (GWAS) have provided novel insight into the genetic architecture of various complex traits; however, this insight has been primarily focused on populations of European descent. This emphasis on European populations has led to individuals of recent African descent being grossly underrepresented in the study of genetics. With African Americans making up less than 2% of participants in neuropsychiatric GWAS, this discrepancy is magnified in diseases such as schizophrenia and bipolar disorder. In this study, we performed GWAS and the gene-based association method PrediXcan for schizophrenia (n = 2,256) and bipolar disorder (n = 1,019) in African American cohorts. In our PrediXcan analyses, we identified PRMT7 (P = 5.5 × 10−6, local false sign rate = 0.12) as significantly associated with schizophrenia following an adaptive shrinkage multiple testing adjustment. This association with schizophrenia was confirmed in the much larger, predominantly European, Psychiatric Genomics Consortium. In addition to the PRMT7 association with schizophrenia, we identified rs10168049 (P = 1.0 × 10−6) as a potential candidate locus for bipolar disorder with highly divergent allele frequencies across populations, highlighting the need for diversity in genetic studies.

scholarly journals Transcriptome association studies of neuropsychiatric traits in African Americans implicate PRMT7 in schizophrenia

2019 ◽  
Author(s):  
Peter N. Fiorica ◽  
Heather E. Wheeler
Keyword(s):  
Bipolar Disorder ◽  
African Americans ◽  
Complex Traits ◽  
Multiple Testing ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Potential Candidate ◽  
Candidate Locus ◽  
Genome Wide ◽  
Multiple Testing Adjustment

ABSTRACTIn the past fifteen years, genome-wide association studies (GWAS) have provided novel insight into the genetic architecture of various complex traits; however, this insight has been primarily focused on populations of European descent. This emphasis on European populations has led to individuals of recent African descent being grossly underrepresented in the study of genetics. With African Americans making up less than two percent of participants in neuropsychiatric GWAS, this discrepancy is magnified in diseases such as schizophrenia and bipolar disorder. In this study, we performed GWAS and the gene-based association method PrediXcan for schizophrenia (n=2,256) and bipolar disorder (n=1,019) in African American cohorts. In our PrediXcan analyses, we identified PRMT7 (P = 5.5 × 10−6, local false sign rate = 0.12) as significantly associated with schizophrenia following an adaptive shrinkage multiple testing adjustment. This association with schizophrenia was confirmed in the much larger, predominantly European, Psychiatric Genomics Consortium. In addition to the PRMT7 association with schizophrenia, we identified rs10168049 (P = 1.0 × 10−6) as a potential candidate locus for bipolar disorder with highly divergent allele frequencies across populations, highlighting the need for diversity in genetic studies.

scholarly journals A meta-analysis of genome-wide association studies of multiple myeloma among men and women of African ancestry

2020 ◽  
Vol 4 (1) ◽  
pp. 181-190 ◽  
Author(s):  
Zhaohui Du ◽  
Niels Weinhold ◽  
Gregory Chi Song ◽  
Kristin A. Rand ◽  
David J. Van Den Berg ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Association Studies ◽  
Meta Analysis ◽  
African Ancestry ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Admixture Mapping ◽  
Genome Wide Association Studies ◽  
Risk Alleles ◽  
Genome Wide

Abstract Persons of African ancestry (AA) have a twofold higher risk for multiple myeloma (MM) compared with persons of European ancestry (EA). Genome-wide association studies (GWASs) support a genetic contribution to MM etiology in individuals of EA. Little is known about genetic risk factors for MM in individuals of AA. We performed a meta-analysis of 2 GWASs of MM in 1813 cases and 8871 controls and conducted an admixture mapping scan to identify risk alleles. We fine-mapped the 23 known susceptibility loci to find markers that could better capture MM risk in individuals of AA and constructed a polygenic risk score (PRS) to assess the aggregated effect of known MM risk alleles. In GWAS meta-analysis, we identified 2 suggestive novel loci located at 9p24.3 and 9p13.1 at P < 1 × 10−6; however, no genome-wide significant association was noted. In admixture mapping, we observed a genome-wide significant inverse association between local AA at 2p24.1-23.1 and MM risk in AA individuals. Of the 23 known EA risk variants, 20 showed directional consistency, and 9 replicated at P < .05 in AA individuals. In 8 regions, we identified markers that better capture MM risk in persons with AA. AA individuals with a PRS in the top 10% had a 1.82-fold (95% confidence interval, 1.56-2.11) increased MM risk compared with those with average risk (25%-75%). The strongest functional association was between the risk allele for variant rs56219066 at 5q15 and lower ELL2 expression (P = 5.1 × 10−12). Our study shows that common genetic variation contributes to MM risk in individuals with AA.

scholarly journals Genome-wide analyses of multiple obesity-related cytokines and hormones informs biology of cardiometabolic traits

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Karlijn A. C. Meeks ◽  
Amy R. Bentley ◽  
Mateus H. Gouveia ◽  
Guanjie Chen ◽  
Jie Zhou ◽  
...  
Keyword(s):  
African Americans ◽  
Association Studies ◽  
African Ancestry ◽  
Interleukin 1 ◽  
Genetic Regulation ◽  
Interleukin 10 ◽  
Genome Wide Association Studies ◽  
Plasminogen Activator Inhibitor 1 ◽  
Genome Wide ◽  
Cardiometabolic Traits

Abstract Background A complex set of perturbations occur in cytokines and hormones in the etiopathogenesis of obesity and related cardiometabolic conditions such as type 2 diabetes (T2D). Evidence for the genetic regulation of these cytokines and hormones is limited, particularly in African-ancestry populations. In order to improve our understanding of the biology of cardiometabolic traits, we investigated the genetic architecture of a large panel of obesity- related cytokines and hormones among Africans with replication analyses in African Americans. Methods We performed genome-wide association studies (GWAS) in 4432 continental Africans, enrolled from Ghana, Kenya, and Nigeria as part of the Africa America Diabetes Mellitus (AADM) study, for 13 obesity-related cytokines and hormones, including adipsin, glucose-dependent insulinotropic peptide (GIP), glucagon-like peptide-1 (GLP-1), interleukin-1 receptor antagonist (IL1-RA), interleukin-6 (IL-6), interleukin-10 (IL-10), leptin, plasminogen activator inhibitor-1 (PAI-1), resistin, visfatin, insulin, glucagon, and ghrelin. Exact and local replication analyses were conducted in African Americans (n = 7990). The effects of sex, body mass index (BMI), and T2D on results were investigated through stratified analyses. Results GWAS identified 39 significant (P value < 5 × 10−8) loci across all 13 traits. Notably, 14 loci were African-ancestry specific. In this first GWAS for adipsin and ghrelin, we detected 13 and 4 genome-wide significant loci respectively. Stratified analyses by sex, BMI, and T2D showed a strong effect of these variables on detected loci. Eight novel loci were successfully replicated: adipsin (3), GIP (1), GLP-1 (1), and insulin (3). Annotation of these loci revealed promising links between these adipocytokines and cardiometabolic outcomes as illustrated by rs201751833 for adipsin and blood pressure and locus rs759790 for insulin level and T2D in lean individuals. Conclusions Our study identified genetic variants underlying variation in multiple adipocytokines, including the first loci for adipsin and ghrelin. We identified population differences in variants associated with adipocytokines and highlight the importance of stratification for discovery of loci. The high number of African-specific loci detected emphasizes the need for GWAS in African-ancestry populations, as these loci could not have been detected in other populations. Overall, our work contributes to the understanding of the biology linking adipocytokines to cardiometabolic traits.

scholarly journals Theoretical and empirical quantification of the accuracy of polygenic scores in ancestry divergent populations

2020 ◽  
Author(s):  
Ying Wang ◽  
Jing Guo ◽  
Guiyan Ni ◽  
Jian Yang ◽  
Peter M. Visscher ◽  
...  
Keyword(s):  
Complex Traits ◽  
Association Studies ◽  
African Ancestry ◽  
Real Data ◽  
European Ancestry ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Polygenic Scores ◽  
Causal Variants ◽  
The Uk

AbstractPolygenic scores (PGS) have been widely used to predict complex traits and risk of diseases using variants identified from genome-wide association studies (GWASs). To date, most GWASs have been conducted in populations of European ancestry, which limits the use of GWAS-derived PGS in non-European populations. Here, we develop a new theory to predict the relative accuracy (RA, relative to the accuracy in populations of the same ancestry as the discovery population) of PGS across ancestries. We used simulations and real data from the UK Biobank to evaluate our results. We found across various simulation scenarios that the RA of PGS based on trait-associated SNPs can be predicted accurately from modelling linkage disequilibrium (LD), minor allele frequencies (MAF), cross-population correlations of SNP effect sizes and heritability. Altogether, we find that LD and MAF differences between ancestries explain alone up to ~70% of the loss of RA using European-based PGS in African ancestry for traits like body mass index and height. Our results suggest that causal variants underlying common genetic variation identified in European ancestry GWASs are mostly shared across continents.

scholarly journals Refining genome-wide associated loci for serum uric acid in individuals with African ancestry

2019 ◽  
Vol 29 (3) ◽  
pp. 506-514
Author(s):  
Guanjie Chen ◽  
Daniel Shriner ◽  
Ayo P Doumatey ◽  
Jie Zhou ◽  
Amy R Bentley ◽  
...  
Keyword(s):  
Uric Acid ◽  
African Americans ◽  
Serum Uric Acid ◽  
Functional Annotation ◽  
Association Studies ◽  
African Ancestry ◽  
Causal Variant ◽  
Conditional Analysis ◽  
Genome Wide Association Studies ◽  
Genome Wide

Abstract Objective Serum uric acid is the end-product of purine metabolism and at high levels is a risk factor for several human diseases including gout and cardiovascular disease. Heritability estimates range from 0.32 to 0.63. Genome-wide association studies (GWAS) provide an unbiased approach to identify loci influencing serum uric acid. Here, we performed the first GWAS for serum uric acid in continental Africans, with replication in African Americans. Methods Africans (n = 4126) and African Americans (n = 5007) were genotyped on high-density GWAS arrays. Efficient mixed model association, a variance component approach, was used to perform association testing for a total of ~ 18 million autosomal genotyped and imputed variants. CAVIARBF was used to fine map significant regions. Results We identified two genome-wide significant loci: 4p16.1 (SLC2A9) and 11q13.1 (SLC22A12). At SLC2A9, the most strongly associated SNP was rs7683856 (P = 1.60 × 10−44). Conditional analysis revealed a second signal indexed by rs6838021 (P = 5.75 × 10−17). Gene expression and regulatory motif data prioritized a single-candidate causal variant for each signal. At SLC22A12, the most strongly associated SNP was rs147647315 (P = 6.65 × 10−25). Conditional analysis and functional annotation prioritized the missense variant rs147647315 (R (Arg) &gt; H (His)) as the sole causal variant. Functional annotation of these three signals implicated processes in skeletal muscle, subcutaneous adipose tissue and the kidneys, respectively. Conclusions This first GWAS of serum uric acid in continental Africans identified three associations at two loci, SLC2A9 and SLC22A12. The combination of weak linkage disequilibrium in Africans and functional annotation led to the identification of candidate causal SNPs for all three signals. Each candidate causal variant implicated a different cell type. Collectively, the three associations accounted for 4.3% of the variance of serum uric acid.

scholarly journals Genome-wide admixture mapping of eGFR and CKD identify European and African ancestry-of-origin loci in U.S. Hispanics/Latinos

2021 ◽  
Author(s):  
Andrea R.V.R. Horimoto ◽  
Jianwen Cai ◽  
James P. Lash ◽  
Martha L. Daviglus ◽  
Nora Franceschini ◽  
...  
Keyword(s):  
African Americans ◽  
Complex Traits ◽  
African Ancestry ◽  
Genetic Ancestry ◽  
European Ancestry ◽  
Health Study ◽  
Admixture Mapping ◽  
Chromosome 14 ◽  
Genome Wide ◽  
Increased Risk

Background Admixture mapping is a powerful approach for gene mapping of complex traits that leverages the diverse genetic ancestry in populations with recent admixture such as U.S. Hispanics/Latinos (HL), who have increased risk of chronic kidney disease (CKD). Methods Genome-wide admixture mapping was performed for CKD and estimated glomerular filtration rate (eGFR) in a sample of 12601 participants from the Hispanic Community Health Study/Study of Latinos, with validation in a sample of 8191 African Americans from the Women's Health Initiative (WHI). Results Three novel ancestry-of-origin loci were identified on chromosomes 2, 14 and 15 for CKD and eGFR. The chromosome 2 locus (2p16.3) consisted of two European ancestry regions encompassing the FSHR and NRXN1 genes, with European ancestry at this locus associated with increased risk for CKD. The chromosome 14 locus (14q32.2) located within the DLK1-DIO3 imprinted domain was driven by European ancestry, and was associated with lower eGFR. The chromosome 15 locus (15q13.3-14) included intronic variants of RYR3 and was within an African-specific genomic region that was associated with higher eGFR. These findings were compared to the conventional genome-wide association study that failed to identify significant associations in these regions. We validated the chromosome 14 and 15 loci for eGFR in the WHI African Americans. Conclusions This study provides evidence of shared ancestry-specific genomic regions influencing eGFR in HL and African Americans, and illustrates the potential for leveraging genetic ancestry in recently admixed populations for novel discovery of kidney trait loci.

scholarly journals Genetics of complex traits: prediction of phenotype, identification of causal polymorphisms and genetic architecture

2016 ◽  
Vol 283 (1835) ◽  
pp. 20160569 ◽  
Author(s):  
M. E. Goddard ◽  
K. E. Kemper ◽  
I. M. MacLeod ◽  
A. J. Chamberlain ◽  
B. J. Hayes
Keyword(s):  
Complex Traits ◽  
Genetic Architecture ◽  
Quantitative Traits ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Crop Breeding ◽  
Single Nucleotide ◽  
Genome Wide ◽  
Phenotype Identification

Complex or quantitative traits are important in medicine, agriculture and evolution, yet, until recently, few of the polymorphisms that cause variation in these traits were known. Genome-wide association studies (GWAS), based on the ability to assay thousands of single nucleotide polymorphisms (SNPs), have revolutionized our understanding of the genetics of complex traits. We advocate the analysis of GWAS data by a statistical method that fits all SNP effects simultaneously, assuming that these effects are drawn from a prior distribution. We illustrate how this method can be used to predict future phenotypes, to map and identify the causal mutations, and to study the genetic architecture of complex traits. The genetic architecture of complex traits is even more complex than previously thought: in almost every trait studied there are thousands of polymorphisms that explain genetic variation. Methods of predicting future phenotypes, collectively known as genomic selection or genomic prediction, have been widely adopted in livestock and crop breeding, leading to increased rates of genetic improvement.

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