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- Mahajan, Anubha, et al.
(författare)
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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
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Tidskriftsartikel (refereegranskat)abstract
- We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
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- Hassan, Ayah M., et al.
(författare)
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Molecular Characterization of Newly Emerging Foot-and-Mouth Disease Virus Serotype SAT 2 of Lib-12 Lineage Isolated from Egypt
- 2022
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Ingår i: Virus Research. - : Elsevier. - 0168-1702 .- 1872-7492. ; 311
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Tidskriftsartikel (refereegranskat)abstract
- An outbreak of foot-and-mouth disease virus (FMDV) serotype SAT 2 occurred in Egypt in 2018, which affected cattle and water buffalo. Previous phylogenetic studies on FMDV circulating in Egypt have mainly focused on genomic regions encoding structural proteins which determine FMDV serotype. So far, none of these studies have analyzed the open reading frame (ORF) sequence of Egyptian SAT 2/Lib-12 lineage. The present study aimed to analyze and identify the ORF genome sequence of Lib-12 lineage which belongs to FMDV serotype SAT 2 topotype VII in Egypt. The protocol workflow was optimized and tested using a representative field isolate of FMDV/ SAT 2/Lib-12 from a bovine tongue sample collected in 2018 from Ismailia governorate (SAT2/EGY/Ismailia/ 2018). The protocol was based on reverse transcription polymerase chain reaction with multiple overlapping primers, amplicons sequencing, and assembly to complete the ORF consensus sequence. Alignments of the sequence fragments formed consensus genome sequence of 7219 nucleotides in length. The complete nucleotide sequence of the Egyptian isolate was related to Ethiopian, Nigerian, and Ghanaian strains, with identity not exceeding 95%. The divergence in the genetic identity of the Egyptian SAT 2/Lib-12 lineage from other Egyptian strains and Libyan isolates was 7%, and this may be attributed to the absence of the Lib-12 lineage ORF sequence from Egypt and Libya in the database. The present study significantly advances knowledge of the molecular analysis of FMDV SAT 2 and the design of vaccine selection for FMDV SAT 2 in Egypt. The study protocol could be applied to other FMDV serotypes.
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