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Sökning: WFRF:(Gao Xiaoyi)

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  • Chasman, Daniel I., et al. (författare)
  • Integration of genome-wide association studies with biological knowledge identifies six novel genes related to kidney function
  • 2012
  • Ingår i: Human Molecular Genetics. - 0964-6906 .- 1460-2083. ; 21:24, s. 5329-5343
  • Tidskriftsartikel (refereegranskat)abstract
    • In conducting genome-wide association studies (GWAS), analytical approaches leveraging biological information may further understanding of the pathophysiology of clinical traits. To discover novel associations with estimated glomerular filtration rate (eGFR), a measure of kidney function, we developed a strategy for integrating prior biological knowledge into the existing GWAS data for eGFR from the CKDGen Consortium. Our strategy focuses on single nucleotide polymorphism (SNPs) in genes that are connected by functional evidence, determined by literature mining and gene ontology (GO) hierarchies, to genes near previously validated eGFR associations. It then requires association thresholds consistent with multiple testing, and finally evaluates novel candidates by independent replication. Among the samples of European ancestry, we identified a genome-wide significant SNP in FBXL20 (P 5.6 10(9)) in meta-analysis of all available data, and additional SNPs at the INHBC, LRP2, PLEKHA1, SLC3A2 and SLC7A6 genes meeting multiple-testing corrected significance for replication and overall P-values of 4.5 10(4)2.2 10(7). Neither the novel PLEKHA1 nor FBXL20 associations, both further supported by association with eGFR among African Americans and with transcript abundance, would have been implicated by eGFR candidate gene approaches. LRP2, encoding the megalin receptor, was identified through connection with the previously known eGFR gene DAB2 and extends understanding of the megalin system in kidney function. These findings highlight integration of existing genome-wide association data with independent biological knowledge to uncover novel candidate eGFR associations, including candidates lacking known connections to kidney-specific pathways. The strategy may also be applicable to other clinical phenotypes, although more testing will be needed to assess its potential for discovery in general.
  • Gao, Yaqing, et al. (författare)
  • Association of iron supplementation and deworming with early childhood development : analysis of Demographic and Health Surveys in ten low- and middle-income countries.
  • 2021
  • Ingår i: European Journal of Nutrition. - 1436-6207 .- 1436-6215.
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: We assessed the associations of iron supplementation and deworming separately or combined with improved early childhood development (ECD) status.METHODS: Cross-sectional data were analyzed for 29,729 children aged 36-59 months surveyed using the Demographic and Health Surveys in ten low- and middle-income countries, where iron supplementation and deworming are recommended by the World Health Organization. In each country, we estimated linear regression models for the effects of iron supplementation and deworming individually or combined on the Early Childhood Development Index (ECDI) z score, and whether this association differed between various ECD domains and the sex and residence of the child. Estimates were pooled using random-effects meta-analyses.RESULTS: Compared with receiving neither of the two interventions, iron supplementation plus deworming was associated with an increased ECDI z score (β = 0.13, 95% confidence interval (CI) 0.03-0.22, p = 0.009), particularly in rural residences. However, iron supplementation and deworming, individually, were not associated with the ECDI z score. Iron supplementation plus deworming was associated with higher odds of on-track development in literacy-numeracy (OR = 1.57, 95% CI 1.24-2.01, p < 0.001) and learning domains (OR = 1.27, 95% CI 1.09-1.48, p = 0.003), but not with development in the social-emotional and physical domains.CONCLUSION: Iron supplementation plus deworming, particularly for populations who are more susceptible to iron deficiency and intestinal worm infections, could be an important intervention for improving ECD. These findings may inform the argument for the necessity of implementing iron supplementation and deworming for preschool-age children.
  • Heard-Costa, Nancy L, et al. (författare)
  • NRXN3 is a novel locus for waist circumference : a genome-wide association study from the CHARGE Consortium
  • 2009
  • Ingår i: PLoS genetics. - 1553-7404. ; 5:6, s. e1000539-
  • Tidskriftsartikel (refereegranskat)abstract
    • Central abdominal fat is a strong risk factor for diabetes and cardiovascular disease. To identify common variants influencing central abdominal fat, we conducted a two-stage genome-wide association analysis for waist circumference (WC). In total, three loci reached genome-wide significance. In stage 1, 31,373 individuals of Caucasian descent from eight cohort studies confirmed the role of FTO and MC4R and identified one novel locus associated with WC in the neurexin 3 gene [NRXN3 (rs10146997, p = 6.4×10−7)]. The association with NRXN3 was confirmed in stage 2 by combining stage 1 results with those from 38,641 participants in the GIANT consortium (p = 0.009 in GIANT only, p = 5.3×10−8 for combined analysis, n = 70,014). Mean WC increase per copy of the G allele was 0.0498 z-score units (0.65 cm). This SNP was also associated with body mass index (BMI) [p = 7.4×10−6, 0.024 z-score units (0.10 kg/m2) per copy of the G allele] and the risk of obesity (odds ratio 1.13, 95% CI 1.07–1.19; p = 3.2×10−5 per copy of the G allele). The NRXN3 gene has been previously implicated in addiction and reward behavior, lending further evidence that common forms of obesity may be a central nervous system-mediated disorder. Our findings establish that common variants in NRXN3 are associated with WC, BMI, and obesity.
  • Köttgen, Anna, et al. (författare)
  • New loci associated with kidney function and chronic kidney disease
  • 2010
  • Ingår i: Nature Genetics. - 1061-4036 .- 1546-1718. ; 42:5, s. 376-384
  • Tidskriftsartikel (refereegranskat)abstract
    • Chronic kidney disease (CKD) is a significant public health problem, and recent genetic studies have identified common CKD susceptibility variants. The CKDGen consortium performed a meta-analysis of genome-wide association data in 67,093 individuals of European ancestry from 20 predominantly population-based studies in order to identify new susceptibility loci for reduced renal function as estimated by serum creatinine (eGFRcrea), serum cystatin c (eGFRcys) and CKD (eGFRcrea < 60 ml/min/1.73 m2; n = 5,807 individuals with CKD (cases)). Follow-up of the 23 new genome-wide–significant loci (P < 5 × 10−8) in 22,982 replication samples identified 13 new loci affecting renal function and CKD (in or near LASS2, GCKR, ALMS1, TFDP2, DAB2, SLC34A1, VEGFA, PRKAG2, PIP5K1B, ATXN2, DACH1, UBE2Q2 and SLC7A9) and 7 loci suspected to affect creatinine production and secretion (CPS1, SLC22A2, TMEM60, WDR37, SLC6A13, WDR72 and BCAS3). These results further our understanding of the biologic mechanisms of kidney function by identifying loci that potentially influence nephrogenesis, podocyte function, angiogenesis, solute transport and metabolic functions of the kidney.
  • Pattaro, Cristian, et al. (författare)
  • Genome-Wide Association and Functional Follow-Up Reveals New Loci for Kidney Function
  • 2012
  • Ingår i: PLoS Genetics. - 1553-7390. ; 8:3, s. e1002584-
  • Tidskriftsartikel (refereegranskat)abstract
    • Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genomewide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD.
  • Zhang, Guiling, et al. (författare)
  • Understanding the influence of alendronate on the morphology and phase transformation of apatitic precursor nanocrystals
  • 2012
  • Ingår i: Journal of Inorganic Biochemistry. - 0162-0134 .- 1873-3344. ; 113, s. 1-8
  • Tidskriftsartikel (refereegranskat)abstract
    • Bisphosphonates (BPs) are a class of synthetic pyrophosphate analogs that can prevent the loss of bone mass, given orally to treat postmenopuasal osteoporosis. It is not clear yet if the benefits of BPs include the possibility of affecting bone apatitic precursors transition for bone consolidation except for encouraging osteoclasts to undergo apoptosis. Furthermore, the complexity of the in vivo system makes it difficult to isolate and study such extracellular topographical cues that trigger bone turnover response. Herein, we proposed a wet-chemical approach employing alendronate sodium (AS) as a guide of hydroxyapatite (HA) precursor growth and conversion which was initiated from the nucleantion of octacalcium phosphate (OCP) in a cell membrane-mimicking surfactant micelle aqueous system. The nanocrystal clusters of dicalcium phosphate dihydrate (DCPD) and OCP nanocryatals were readily precipitated within a relatively narrow AS concentration range (2-8 mu M). However, such low concentrations of AS seemed to stabilize the more acidic phases, and to delay the transformation into HA, to an extent which increased on increasing AS concentration. In contrast, at a slight higher concentrations (16-32 mu M), AS promoted HA precipitation after ageing for 1 h. It was found that the effect of AS on the phase selectivity of apatitic precursors was concentration-dependent within a prolonged ageing time stage (0.5-168 h). The AS-assisted reactions in vitro offer an expedient way to understand the underlying implementarity between bone and BPs for bone consolidation, and to improve our understanding of benefit of BP dosages on bone turnover and trauma healing.
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