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Träfflista för sökning "WFRF:(Jia Weiping) "

Sökning: WFRF:(Jia Weiping)

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1.
  • Cho, Yoon Shin, et al. (författare)
  • Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians.
  • 2012
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We conducted a three-stage genetic study to identify susceptibility loci for type 2 diabetes (T2D) in east Asian populations. We followed our stage 1 meta-analysis of eight T2D genome-wide association studies (6,952 cases with T2D and 11,865 controls) with a stage 2 in silico replication analysis (5,843 cases and 4,574 controls) and a stage 3 de novo replication analysis (12,284 cases and 13,172 controls). The combined analysis identified eight new T2D loci reaching genome-wide significance, which mapped in or near GLIS3, PEPD, FITM2-R3HDML-HNF4A, KCNK16, MAEA, GCC1-PAX4, PSMD6 and ZFAND3. GLIS3, which is involved in pancreatic beta cell development and insulin gene expression, is known for its association with fasting glucose levels. The evidence of an association with T2D for PEPD and HNF4A has been shown in previous studies. KCNK16 may regulate glucose-dependent insulin secretion in the pancreas. These findings, derived from an east Asian population, provide new perspectives on the etiology of T2D.
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2.
  • Flannick, Jason, et al. (författare)
  • Data Descriptor : Sequence data and association statistics from 12,940 type 2 diabetes cases and controls
  • 2017
  • Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4
  • Tidskriftsartikel (refereegranskat)abstract
    • To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (> 80% of low-frequency coding variants in similar to ~82 K Europeans via the exome chip, and similar to ~90% of low-frequency non-coding variants in similar to ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.
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3.
  • Fuchsberger, Christian, et al. (författare)
  • The genetic architecture of type 2 diabetes
  • 2016
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7614, s. 41-47
  • Tidskriftsartikel (refereegranskat)abstract
    • The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.
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4.
  • Leung, Howell, et al. (författare)
  • Risk assessment with gut microbiome and metabolite markers in NAFLD development
  • 2022
  • Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 14:648, s. eabk0855-
  • Tidskriftsartikel (refereegranskat)abstract
    • A growing body of evidence suggests interplay between the gut microbiota and the pathogenesis of nonalcoholic fatty liver disease (NAFLD). However, the role of the gut microbiome in early detection of NAFLD is unclear. Prospective studies are necessary for identifying reliable, microbiome markers for early NAFLD. We evaluated 2487 individuals in a community-based cohort who were followed up 4.6 years after initial clinical examination and biospecimen sampling. Metagenomic and metabolomic characterizations using stool and serum samples taken at baseline were performed for 90 participants who progressed to NAFLD and 90 controls who remained NAFLD free at the follow-up visit. Cases and controls were matched for gender, age, body mass index (BMI) at baseline and follow-up, and 4-year BMI change. Machine learning models integrating baseline microbial signatures (14 features) correctly classified participants (auROCs of 0.72 to 0.80) based on their NAFLD status and liver fat accumulation at the 4-year follow up, outperforming other prognostic clinical models (auROCs of 0.58 to 0.60). We confirmed the biological relevance of the microbiome features by testing their diagnostic ability in four external NAFLD case-control cohorts examined by biopsy or magnetic resonance spectroscopy, from Asia, Europe, and the United States. Our findings raise the possibility of using gut microbiota for early clinical warning of NAFLD development.
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5.
  • Manning, Alisa, et al. (författare)
  • A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk
  • 2017
  • Ingår i: Diabetes. - : AMER DIABETES ASSOC. - 0012-1797 .- 1939-327X. ; 66:7, s. 2019-2032
  • Tidskriftsartikel (refereegranskat)abstract
    • To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting plasma insulin (FI), a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in FI levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-h insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio 1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function. We extend the allelic spectrum for coding variants in AKT2 associated with disorders of glucose homeostasis and demonstrate bidirectional effects of variants within the pleckstrin homology domain of AKT2.
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6.
  • Todd, Jennifer N., et al. (författare)
  • Variation in Glucose Homeostasis Traits Associated With P2RX7 Polymorphisms in Mice and Humans
  • 2015
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 100:5, s. 688-696
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Extracellular nucleotide receptors are expressed in pancreatic B-cells. Purinergic signaling via these receptors may regulate pancreatic B-cell function. Objective: We hypothesized that purinergic signaling might influence glucose regulation and sought evidence in human studies of glycemic variation and a mouse model of purinergic signaling dysfunction. Design: In humans, we mined genome-wide meta-analysis data sets to examine purinergic signaling genes for association with glycemic traits and type 2 diabetes. We performed additional testing in two genomic regions (P2RX4/P2RX7 and P2RY1) in a cohort from the Prevalence, Prediction, and Prevention of Diabetes in Botnia (n = 3504), which includes more refined measures of glucose homeostasis. In mice, we generated a congenic model of purinergic signaling dysfunction by crossing the naturally hypomorphic C57BL6 P2rx7 allele onto the 129SvJ background. Results: Variants in five genes were associated with glycemic traits and in three genes with diabetes risk. In the Prevalence, Prediction, and Prevention of Diabetes in Botnia study, the minor allele in the missense functional variant rs1718119 (A348T) in P2RX7 was associated with increased insulin sensitivity and secretion, consistent with its known effect on increased pore function. Both male and female P2x7-C57 mice demonstrated impaired glucose tolerance compared with matched P2x7-129 mice. Insulin tolerance testing showed that P2x7-C57 mice were also less responsive to insulin than P2x7-129 mice. Conclusions: We show association of the purinergic signaling pathway in general and hypofunctioning P2X7 variants in particular with impaired glucose homeostasis in both mice and humans.
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