63 research outputs found

    Minority-centric meta-analyses of blood lipid levels identify novel loci in the Population Architecture using Genomics and Epidemiology (PAGE) study

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    Lipid levels are important markers for the development of cardio-metabolic diseases. Although hundreds of associated loci have been identified through genetic association studies, the contribution of genetic factors to variation in lipids is not fully understood, particularly in U.S. minority groups. We performed genome-wide association analyses for four lipid traits in over 45,000 ancestrally diverse participants from the Population Architecture using Genomics and Epidemiology (PAGE) Study, followed by a meta-analysis with several European ancestry studies. We identified nine novel lipid loci, five of which showed evidence of replication in independent studies. Furthermore, we discovered one novel gene in a PrediXcan analysis, minority-specific independent signals at eight previously reported loci, and potential functional variants at two known loci through fine-mapping. Systematic examination of known lipid loci revealed smaller effect estimates in African American and Hispanic ancestry populations than those in Europeans, and better performance of polygenic risk scores based on minority-specific effect estimates. Our findings provide new insight into the genetic architecture of lipid traits and highlight the importance of conducting genetic studies in diverse populations in the era of precision medicine

    Magnetic shear effect on plasma transport at Te/Ti ~ 1 through electron cyclotron heating in DIII-D plasmas

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    The effect of magnetic shear on plasma transport for an electron to ion temperature ratio (Te/Ti) near unity has been explored in DIII-D utilizing electron cyclotron heating (ECH). Previous reports showed that significant confinement degradation occurred at Te/Ti ~ 1 in positive shear (PS) plasmas in DIII-D, whereas reduced confinement degradation was observed in negative central shear (NCS) plasmas. In this study, plasma transport in weak magnetic shear (WS) plasmas with ECH is investigated and compared with that in NCS and PS plasmas. Here the magnetic shears (s^\hat s) are s^\hat s > 0.5, ~0 and <-0.1 in the core region (ρ~ 0.3–0.4) of PS, WS and NCS plasmas, respectively, and flat or negative inside ρ~ 0.4 in the WS and NCS plasmas. Weak magnetic shear is found to be effective in minimizing degradation of ion thermal confinement as Te/Ti increases through ECH application, and an improved confinement factor of H98y2 ~ 1.2 is maintained, similar to NCS plasmas. At Te/Ti ~ 1, the ion thermal diffusivity around an internal transport barrier decreases when changing the magnetic shear from positive to weak or negative shear. Also, reduced local particle and momentum transport was indicated by steeper density and toroidal rotation profiles in the weak and negative shear regimes. Linear gyrokinetic simulations predict little change in growth rates of low-k turbulence with ECH application in the WS and NCS plasmas, which is consistent with the transport and profile analyses
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