ORCID Profile
0000-0002-1770-5993
Current Organisations
University of North Carolina
,
University of California
,
Universiti Putra Malaysia
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Publisher: American Society of Hematology
Date: 14-01-2020
DOI: 10.1182/BLOODADVANCES.2019000491
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 in iduals of EA. Little is known about genetic risk factors for MM in in iduals 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 in iduals 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 in iduals. Of the 23 known EA risk variants, 20 showed directional consistency, and 9 replicated at P & .05 in AA in iduals. In 8 regions, we identified markers that better capture MM risk in persons with AA. AA in iduals 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 in iduals with AA.
Publisher: American Association for Cancer Research (AACR)
Date: 12-2016
DOI: 10.1158/1055-9965.EPI-15-1193
Abstract: Background: Genome-wide association studies (GWAS) in European populations have identified genetic risk variants associated with multiple myeloma. Methods: We performed association testing of common variation in eight regions in 1,318 patients with multiple myeloma and 1,480 controls of European ancestry and 1,305 patients with multiple myeloma and 7,078 controls of African ancestry and conducted a meta-analysis to localize the signals, with epigenetic annotation used to predict functionality. Results: We found that variants in 7p15.3, 17p11.2, 22q13.1 were statistically significantly (P & 0.05) associated with multiple myeloma risk in persons of African ancestry and persons of European ancestry, and the variant in 3p22.1 was associated in European ancestry only. In a combined African ancestry–European ancestry meta-analysis, variation in five regions (2p23.3, 3p22.1, 7p15.3, 17p11.2, 22q13.1) was statistically significantly associated with multiple myeloma risk. In 3p22.1, the correlated variants clustered within the gene body of ULK4. Correlated variants in 7p15.3 clustered around an enhancer at the 3′ end of the CDCA7L transcription termination site. A missense variant at 17p11.2 (rs34562254, Pro251Leu, OR, 1.32 P = 2.93 × 10−7) in TNFRSF13B encodes a lymphocyte-specific protein in the TNF receptor family that interacts with the NF-κB pathway. SNPs correlated with the index signal in 22q13.1 cluster around the promoter and enhancer regions of CBX7. Conclusions: We found that reported multiple myeloma susceptibility regions contain risk variants important across populations, supporting the use of multiple racial/ethnic groups with different underlying genetic architecture to enhance the localization and identification of putatively functional alleles. Impact: A subset of reported risk loci for multiple myeloma has consistent effects across populations and is likely to be functional. Cancer Epidemiol Biomarkers Prev 25(12) 1609–18. ©2016 AACR.
Publisher: CSIRO Publishing
Date: 2019
DOI: 10.1071/IS18065
Abstract: Australia and Southeast Asia are hotspots of global ersity in the fruit-fly genus Bactrocera. Although a great ersity of species has been long recognised, evolutionary relationships are poorly understood, largely because previous sequencing techniques have provided insufficient historical signal for phylogenetic reconstruction. Poorly understood biogeographic history in Bactrocera has prevented a deeper understanding of migratory patterns in this economically important pest group. Using representatives from Australia and Malaysia, we tested the utility of a genome-reduction approach that generates thousands of single-nucleotide polymorphisms for phylogenetic reconstructions. This approach has high utility for species identification because of the ease of s le addition over time, and the species-level specificity able to be achieved with the markers. These data have provided a strongly supported phylogenetic tree congruent with topologies generated using more intensive sequencing approaches. In addition, our results do not support taxonomic assignments to species complex for a number of species, such as B. endiandrae in the dorsalis complex, yet find a close relationship between B. pallida and the dorsalis species. Our data have further validated non-monophyletic evolution of male response to primary attractants. We also showed at least two ersification events between Australia and Southeast Asia, indicating trans-regional dispersal in important pest species.
Publisher: Oxford University Press (OUP)
Date: 23-04-2014
DOI: 10.1093/HMG/DDU183
No related grants have been discovered for Sarah Nyante.