scholarly journals New insights into malaria susceptibility from the genomes of 17,000 individuals from Africa, Asia, and Oceania

2019 ◽  
Author(s):  
Keyword(s):  
Host Resistance ◽  
Genome Wide Association Study ◽  
Future Research ◽  
Human Populations ◽  
Chromosome 6 ◽  
Genetic Determinants ◽  
Transcription Start ◽  
Genome Wide ◽  
A Genome ◽  
Malaria Susceptibility

AbstractWe conducted a genome-wide association study of host resistance to severe Plasmodium falciparum malaria in over 17,000 individuals from 11 malaria-endemic countries, undertaking a wide ranging analysis which identifies five replicable associations with genome-wide levels of evidence. Our findings include a newly implicated variant on chromosome 6 associated with risk of cerebral malaria, and the discovery of an erythroid-specific transcription start site underlying the association in ATP2B4. Previously reported HLA associations cannot be replicated in this dataset. We estimate substantial heritability of severe malaria (h2 ~ 23%), of which around 10% is explained by the currently identified associations. Our dataset will provide a major building block for future research on the genetic determinants of disease in these diverse human populations.

scholarly journals Insights into malaria susceptibility using genome-wide data on 17,000 individuals from Africa, Asia and Oceania

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Keyword(s):  
Severe Malaria ◽  
Genome Wide Association Study ◽  
Causal Mechanism ◽  
Chromosome 6 ◽  
Genetic Determinants ◽  
Genome Wide ◽  
A Genome ◽  
Genome Wide Data ◽  
Candidate Loci ◽  
Population Controls

AbstractThe human genetic factors that affect resistance to infectious disease are poorly understood. Here we report a genome-wide association study in 17,000 severe malaria cases and population controls from 11 countries, informed by sequencing of family trios and by direct typing of candidate loci in an additional 15,000 samples. We identify five replicable associations with genome-wide levels of evidence including a newly implicated variant on chromosome 6. Jointly, these variants account for around one-tenth of the heritability of severe malaria, which we estimate as ~23% using genome-wide genotypes. We interrogate available functional data and discover an erythroid-specific transcription start site underlying the known association in ATP2B4, but are unable to identify a likely causal mechanism at the chromosome 6 locus.  Previously reported HLA associations do not replicate in these samples. This large dataset will provide a foundation for further research on the genetic determinants of malaria resistance in diverse populations.

Genome-Wide Association for HbA1c in Malay Identified Deletion on SLC4A1 that Influences HbA1c Independent of Glycemia

2020 ◽  
Vol 105 (12) ◽  
pp. 3854-3864
Author(s):  
Jin-Fang Chai ◽  
Shih-Ling Kao ◽  
Chaolong Wang ◽  
Victor Jun-Yu Lim ◽  
Ing Wei Khor ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Hba1c Level ◽  
Genome Wide Association Study ◽  
Meta Analysis ◽  
Genome Wide Association ◽  
Specific Reference ◽  
Genetic Determinants ◽  
Genome Wide ◽  
Whole Exome ◽  
A Genome

Abstract Context Glycated hemoglobin A1c (HbA1c) level is used to screen and diagnose diabetes. Genetic determinants of HbA1c can vary across populations and many of the genetic variants influencing HbA1c level were specific to populations. Objective To discover genetic variants associated with HbA1c level in nondiabetic Malay individuals. Design and Participants We conducted a genome-wide association study (GWAS) analysis for HbA1c using 2 Malay studies, the Singapore Malay Eye Study (SiMES, N = 1721 on GWAS array) and the Living Biobank study (N = 983 on GWAS array and whole-exome sequenced). We built a Malay-specific reference panel to impute ethnic-specific variants and validate the associations with HbA1c at ethnic-specific variants. Results Meta-analysis of the 1000 Genomes imputed array data identified 4 loci at genome-wide significance (P < 5 × 10-8). Of the 4 loci, 3 (ADAM15, LINC02226, JUP) were novel for HbA1c associations. At the previously reported HbA1c locus ATXN7L3-G6PC3, association analysis using the exome data fine-mapped the HbA1c associations to a 27-bp deletion (rs769664228) at SLC4A1 that reduced HbA1c by 0.38 ± 0.06% (P = 3.5 × 10-10). Further imputation of this variant in SiMES confirmed the association with HbA1c at SLC4A1. We also showed that these genetic variants influence HbA1c level independent of glucose level. Conclusion We identified a deletion at SLC4A1 associated with HbA1c in Malay. The nonglycemic lowering of HbA1c at rs769664228 might cause individuals carrying this variant to be underdiagnosed for diabetes or prediabetes when HbA1c is used as the only diagnostic test for diabetes.

Abstract 4726: Genetic determinants of serum retinol: A genome-wide association study

2011 ◽  
Author(s):  
Alison M. Mondul ◽  
Kai Yu ◽  
Stephanie J. Weinstein ◽  
Jarmo Virtamo ◽  
Kevin B. Jacobs ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Serum Retinol ◽  
Genetic Determinants ◽  
Genome Wide ◽  
A Genome

scholarly journals European landrace diversity for common bean biofortification: a genome-wide association study

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Leonardo Caproni ◽  
Lorenzo Raggi ◽  
Elise F. Talsma ◽  
Peter Wenzl ◽  
Valeria Negri
Keyword(s):  
Common Bean ◽  
Genome Wide Association Study ◽  
Preliminary Evidence ◽  
Snp Markers ◽  
Genome Wide Association ◽  
Future Research ◽  
Balanced Diet ◽  
Genome Wide ◽  
Seed Content ◽  
A Genome

AbstractMineral deficiencies represent a global challenge that needs to be urgently addressed. An adequate intake of iron and zinc results in a balanced diet that reduces chances of impairment of many metabolic processes that can lead to clinical consequences. In plants, bioavailability of such nutrients is reduced by presence of compounds such as phytic acid, that can chelate minerals and reduce their absorption. Biofortification of common bean (Phaseolus vulgaris L.) represents an important strategy to reduce mineral deficiencies, especially in areas of the world where this crop plays a key role in the diet. In this study, a panel of diversity encompassing 192 homozygous genotypes, was screened for iron, zinc and phytate seed content. Results indicate a broad variation of these traits and allowed the identification of accessions reasonably carrying favourable trait combinations. A significant association between zinc seed content and some molecular SNP markers co-located on the common bean Pv01 chromosome was detected by means of genome-wide association analysis. The gene Phvul001G233500, encoding for an E3 ubiquitin-protein ligase, is proposed to explain detected associations. This result represents a preliminary evidence that can foster future research aiming at understanding the genetic mechanisms behind zinc accumulation in beans.

scholarly journals A genome-wide association study unravels cytokinin as a major component in the root defense responses against Ralstonia solanacearum

2021 ◽  
Author(s):  
Alejandro Alonso-Díaz ◽  
Santosh B Satbhai ◽  
Roger de Pedro-Jové ◽  
Hannah M Berry ◽  
Christian Göschl ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Allelic Variation ◽  
Defense Responses ◽  
Genome Wide Association ◽  
Root Growth Inhibition ◽  
Future Research ◽  
Cytokinin Signaling ◽  
Genome Wide ◽  
A Genome

Abstract Bacterial wilt caused by the soil-borne pathogen Ralstonia solancearum is economically devastating, with no effective methods to fight the disease. This pathogen invades plants through their roots and colonizes their xylem, clogging the vasculature and causing rapid wilting. Key to preventing colonization are the early defense responses triggered in the host’s root upon infection, which remain mostly unknown. Here, we have taken advantage of a high-throughput in vitro infection system to screen natural variability associated to the root growth inhibition phenotype caused by R. solanacearum in Arabidopsis during the first hours of infection. To analyze the genetic determinants of this trait, we have performed a Genome-Wide Association Study, identifying allelic variation at several loci related to cytokinin metabolism, including genes responsible for biosynthesis and degradation of cytokinin. Further, our data clearly demonstrate that cytokinin signaling is induced early during the infection process and cytokinin contributes to immunity against R. solanacearum. This study highlights a new role of cytokinin in root immunity, paving the way for future research that will help understanding the mechanisms underpinning root defenses.

scholarly journals Common Genetic Determinants of Vitamin D Insufficiency: A Genome-Wide Association Study

2011 ◽  
Vol 66 (2) ◽  
pp. 91-93
Author(s):  
Thomas J. Wang ◽  
Feng Zhang ◽  
J. Brent Richards ◽  
Bryan Kestenbaum ◽  
Joyce B. van Meurs ◽  
...  
Keyword(s):  
Vitamin D ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Vitamin D Insufficiency ◽  
Genome Wide Association ◽  
Genetic Determinants ◽  
Genome Wide ◽  
A Genome
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