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Genome-wide association studies (GWAS) have identified ∼100 loci associated with blood lipid levels, but much of the trait heritability remains unexplained, and at most loci the identities of the trait-influencing variants remain unknown. We conducted a trans-ethnic fine-mapping study at 18, 22, and 18 GWAS loci on the Metabochip for their association with triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), respectively, in individuals of African American (n = 6,832), East Asian (n = 9,449), and European (n = 10,829) ancestry. We aimed to identify the variants with strongest association at each locus, identify additional and population-specific signals, refine association signals, and assess the relative significance of previously described functional variants. Among the 58 loci, 33 exhibited evidence of association at P<1×10−4 in at least one ancestry group. Sequential conditional analyses revealed that ten, nine, and four loci in African Americans, Europeans, and East Asians, respectively, exhibited two or more signals. At these loci, accounting for all signals led to a 1.3- to 1.8-fold increase in the explained phenotypic variance compared to the strongest signals. Distinct signals across ancestry groups were identified at PCSK9 and APOA5. Trans-ethnic analyses narrowed the signals to smaller sets of variants at GCKR, PPP1R3B, ABO, LCAT, and ABCA1. Of 27 variants reported previously to have functional effects, 74% exhibited the strongest association at the respective signal. In conclusion, trans-ethnic high-density genotyping and analysis confirm the presence of allelic heterogeneity, allow the identification of population-specific variants, and limit the number of candidate SNPs for functional studies.

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a b s t r a c tThis work designed an ultrasensitive non-enzymatic immunosensor for microcystin-LR (MC-LR) detection using carbon nanofibers (CNFs) as immobilization matrix and gold nanoparticles (AuNPs) as an electrochemical label. The carboxylic group functionalized CNFs could well disperse in water for at least three months, and CNFs modified electrode showed high conductivity and enhanced electron transfer. The immunosensor was constructed by immobilizing MC-LR antigen on CNFs modified electrode. With a competitive immunoassay format, the coated MC-LR antigen competed for MC-LR antibody with added target MC-LR to form antibody-antigen immunocomplex. Subsequently, the immunocomplex reacted with AuNPs labeled secondary antibodies, and the bound AuNPs were finally electro-oxidized in 0.1 M HCl to produce AuCl 4 − for differential pulse voltammetric detection of MC-LR. Under optimal conditions, the immunosensor exhibited a wide linear response to MC-LR ranging from 0.0025 to 5 g L −1 with a detection limit of 1.68 ng L −1 at a signal to noise of 3. This method showed good accuracy, acceptable precision and reproducibility. The assay results of MC-LR in polluted water were in a good agreement with the reference values. The proposed ultrasensitive immunoassay showed the promising application in environmental monitoring and public health.

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Perovskite oxides have attracted great attention in electrochemistry due to their compositional and structural flexibility. Herein, the microwave/ultrasound assisted hydrothermal procedures were developed to synthesize Ce-doped LaCoO3 perovskite oxide as...

Background: High disease burden suggests the desirability to identify high-risk Asian never-smoking females (NSF) who may benefit from low-dose CT (LDCT) screening. In North America, one is eligible for LDCT screening if one satisfies the U.S. Preventive Services Task Force (USPSTF) criteria or has model-estimated 6-year risk greater than 0.0151. According to two U.S. reports, only 36.6% female patients with lung cancer met the USPSTF criteria, while 38% of the ever-smokers ages 55 to 74 years met the USPSTF criteria. Methods: Using data on NSFs in the Taiwan Genetic Epidemiology Study of Lung Adenocarcinoma and the Taiwan Biobank before August 2016, we formed an age-matched case-control study consisting of 1,748 patients with lung cancer and 6,535 controls. Using these and an estimated age-specific lung cancer 6-year incidence rate among Taiwanese NSFs, we developed the Taiwanese NSF Lung Cancer Risk Models using genetic information and simplified questionnaire (TNSF-SQ). Performance evaluation was based on the newer independent datasets: Taiwan Lung Cancer Pharmacogenomics Study (LCPG) and Taiwan Biobank data after August 2016 (TWB2). Results: The AUC based on the NSFs ages 55 to 70 years in LCPG and TWB2 was 0.714 [95% confidence intervals (CI), 0.660-0.768]. For women in TWB2 ages 55 to 70 years, 3.94% (95% CI, 2.95-5.13) had risk higher than 0.0151. For women in LCPG ages 55 to 74 years, 27.03% (95% CI, 19.04-36.28) had risk higher than 0.0151. Conclusions: TNSF-SQ demonstrated good discriminative power. The ability to identify 27.03% of high-risk Asian NSFs ages 55 to 74 years deserves attention. Impact: TNSF-SQ seems potentially useful in selecting Asian NSFs for LDCT screening.