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  • Schork, Andrew J, et al. (författare)
  • All SNPs are not created equal: genome-wide association studies reveal a consistent pattern of enrichment among functionally annotated SNPs.
  • 2013
  • Ingår i: PLoS genetics. - 1553-7404. ; 9:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent results indicate that genome-wide association studies (GWAS) have the potential to explain much of the heritability of common complex phenotypes, but methods are lacking to reliably identify the remaining associated single nucleotide polymorphisms (SNPs). We applied stratified False Discovery Rate (sFDR) methods to leverage genic enrichment in GWAS summary statistics data to uncover new loci likely to replicate in independent samples. Specifically, we use linkage disequilibrium-weighted annotations for each SNP in combination with nominal p-values to estimate the True Discovery Rate (TDR = 1-FDR) for strata determined by different genic categories. We show a consistent pattern of enrichment of polygenic effects in specific annotation categories across diverse phenotypes, with the greatest enrichment for SNPs tagging regulatory and coding genic elements, little enrichment in introns, and negative enrichment for intergenic SNPs. Stratified enrichment directly leads to increased TDR for a given p-value, mirrored by increased replication rates in independent samples. We show this in independent Crohn's disease GWAS, where we find a hundredfold variation in replication rate across genic categories. Applying a well-established sFDR methodology we demonstrate the utility of stratification for improving power of GWAS in complex phenotypes, with increased rejection rates from 20% in height to 300% in schizophrenia with traditional FDR and sFDR both fixed at 0.05. Our analyses demonstrate an inherent stratification among GWAS SNPs with important conceptual implications that can be leveraged by statistical methods to improve the discovery of loci.
  • Yuan, Q., et al. (författare)
  • Automatic robot taping with force feedback
  • 2017
  • Ingår i: 2017 IEEE International Conference on Robotics and Automation (ICRA). - Institute of Electrical and Electronics Engineers (IEEE). - 9781509046331 ; s. 1821-1826
  • Konferensbidrag (refereegranskat)abstract
    • In surface treatment processes like plasma spraying and spray painting of workpieces, protecting the uninvolved surface by applying masking tape is a common process. Due to the operation complexity for different geometries, such taping tasks depend on a lot of manual works, which is tedious and tiring. This paper introduces an automatic agile robotic system and the corresponding algorithm to do the surface taping. The automatic taping system consists of a 3D scanner for workpiece 3D model reconstruction, a taping end-effector which is mounted on a robot manipulator to handle the taping task, and a rotating platform that is used to hold the workpiece. The surface covering method and the taping path planning algorithms using the scanned model are introduced. With the implementation of the compliance mechanism, the force feedback and the tape cutting mechanism, the system is able to tape flat, cylindrical, freeform, and grooved surfaces. Experiments conducted on taping an engine inner liner shows that the surface can be covered with uniform taping overlap and very little wrinkle. The proposed system is a useful taping package for industrial applications such as workpiece repairing and surface protection, where surface treatments are involved.
  • Zhang, R. Y., et al. (författare)
  • Genome-wide study of immune biomarkers in cerebrospinal fluid and serum from patients with bipolar disorder and controls
  • 2020
  • Ingår i: Translational Psychiatry. - 2158-3188. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Bipolar disorder is a common, chronic psychiatric disorder. Despite high heritability, there is a paucity of identified genetic risk factors. Immune biomarkers are under more direct genetic influence than bipolar disorder. To explore the genetic associations with immune biomarker levels in cerebrospinal fluid (CSF) and blood serum which previously showed differences in bipolar disorder, we performed a study involving 291 individuals (184 bipolar disorder patients and 107 controls). The biomarkers assayed in both CSF and serum were: chitinase-3-like protein-1 (YKL-40), monocyte chemoattractant protein-1 (MCP-1), soluble cluster of differentiation (sCD14), tissue inhibitor of metalloproteinases-1 and 2 (TIMP-1 and TIMP-2). C-reactive protein (CRP) was only quantified in serum, and interleukin 8 (IL-8) measures were only available in CSF. Genome-wide association studies were conducted using PLINK for each of three genotyping waves and incorporated covariates for population substructure, age, sex, and body mass index (BMI). Results were combined by meta-analysis. Genome-wide significant associations were detected for all biomarkers except TIMP-1 and TIMP-2 in CSF. The strongest association in CSF was found for markers within the CNTNAP5 gene with YKL-40 (rs150248456, P=2.84x10(-10)). The strongest association in serum was also for YKL-40 but localized to the FANCI gene (rs188263039, P=5.80x10(-26)). This study revealed numerous biologically plausible genetic associations with immune biomarkers in CSF and blood serum. Importantly, the genetic variants regulating immune biomarker levels in CSF and blood serum differ. These results extend our knowledge of how biomarkers showing alterations in bipolar disorder are genetically regulated.
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Landén, Mikael, 1966 ... (146)
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