8 research outputs found
The trans-ancestral genomic architecture of glycemic traits
Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.Diabetes mellitus: pathophysiological changes and therap
The Paleolithic of Dzungaria (Xinjiang, Northwest China) Based on Materials from the Luotuoshi Site
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First Documented Camelus knoblochi Nehring (1901) and Fossil Camelus ferus Przewalski (1878) From Late Pleistocene Archaeological Contexts in Mongolia
Throughout the arid lands of Africa and Eurasia, camelids facilitated the expansion of human populations into areas that would not likely have been habitable without the transportation abilities of this animal along with the organic resources it provides, including dung, meat, milk, leather, wool, and bones. The two-humped, Bactrian, species of Camelus, C. ferus in its wild state and C. bactrianus when domesticated, is much more poorly known in prehistoric archaeological contexts than its single-humped congeneric, C. dromedarius. Our research uses a convergence of evidence approach to analyze reports and remains of Plio-Pleistocene camelids in Central and Northern Asia and trace the latest-known fossil Bactrian relative, Camelus knoblochi, that seems to have survived in the Gobi Desert until the Last Glacial Maximum (ca. 26.5–19 ka). Rock art depictions, some of which may be of Pleistocene age, record the complexity of nascent human-camel interactions and provide the impetus for further archaeological studies of both the origins of C. bactrianus and its increasingly complex relationships with the highly mobile prehistoric peoples of Central and Northern Asia. Copyright © 2022 Klementiev, Khatsenovich, Tserendagva, Rybin, Bazargur, Marchenko, Gunchinsuren, Derevianko and Olsen.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]
The Initial Upper Paleolithic in Northeast Asia : toward the definition of a techno complex.
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Explicit similarities and expected variability : the Initial Upper Paleolithic in Northeast Asia.
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Afontova Gora II archaeological site: Geology and postdepositional deformation (Krasnoyarsk, Siberia)
Smoking-by-genotype interaction in type 2 diabetes risk and fasting glucose
Smoking is a potentially causal behavioral risk factor for type 2 diabetes (T2D), but not all smokers develop T2D. It is unknown whether genetic factors partially explain this variation. We performed genome-environment-wide interaction studies to identify loci exhibiting potential interaction with baseline smoking status (ever vs. never) on incident T2D and fasting glucose (FG). Analyses were performed in participants of European (EA) and African ancestry (AA) separately. Discovery analyses were conducted using genotype data from the 50,000-single-nucleotide polymorphism (SNP) ITMAT-Broad-CARe (IBC) array in 5 cohorts from from the Candidate Gene Association Resource Consortium (n = 23,189). Replication was performed in up to 16 studies from the Cohorts for Heart Aging Research in Genomic Epidemiology Consortium (n = 74,584). In meta-analysis of discovery and replication estimates, 5 SNPs met at least one criterion for potential interaction with smoking on incident T2D at p<1x10-7 (adjusted for multiple hypothesis-testing with the IBC array). Two SNPs had significant joint effects in the overall model and significant main effects only in one smoking stratum: rs140637 (FBN1) in AA individuals had a significant main effect only among smokers, and rs1444261 (closest gene C2orf63) in EA individuals had a significant main effect only among nonsmokers. Three additional SNPs were identified as having potential interaction by exhibiting a significant main effects only in smokers: rs1801232 (CUBN) in AA individuals, rs12243326 (TCF7L2) in EA individuals, and rs4132670 (TCF7L2) in EA individuals. No SNP met significance for potential interaction with smoking on baseline FG. The identification of these loci provides evidence for genetic interactions with smoking exposure that may explain some of the heterogeneity in the association between smoking and T2D.</p