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DTSTART:20190331T030000
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DTSTART:20191027T020000
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DTSTAMP:20260405T004805Z
UID:5d0899223b8e2415447489@ist.ac.at
DTSTART:20190624T110000
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DESCRIPTION:Speaker: Roberto Bonelli\nhosted by Sandra Siegert\nAbstract: M
 acular telangiectasia type 2 (MacTel)\, is a rare degenerative eye disease
 . The first GWA study discovered five loci indicating involvements of the 
 glycine/serine metabolic pathway. Here\, we present a causal model of MacT
 el genetics discovered by integrating different omics data. Using Mendelia
 n Randomization (MR\; 476 MacTel cases\, 1733 controls) we tested the gene
 tic contribution to disease of >140 metabolites and comorbid traits and fo
 und causal effects from serine and glycine (serine: OR=0.5\, P=1.08e-33\; 
 glycine: OR=0.53\, P= 1.31e-25)\, whilst eliminating other spurious metabo
 lites. Serine was found to cause disease progression (b = -0.54\, P = 0.01
 3) based on longitudinal retinal image data for 455 patients. Novel geneti
 c loci were further revealed via conditional GWAS and MTAG (7p11.2\, P=2.2
 E-15\; 3p24.1\, P=3.1e-08\; 19p13.2\, P=6.3e-08). Analyses of serum metabo
 lomics data revealed widespread rewiring of reflecting glycine and serine 
 commensurate with genetic disruption. Lastly\, we confirmed that genetical
 ly induced depletion of serine in MacTel patients likely results in accumu
 lation of deoxy-sphingolipids (MTvsDOXSL b=0.6\, P=2.6e-11\; SERvsDOXSL b=
 -1.27735\, P<2e-16) which appears extremely toxic for retinal and neuronal
  tissues\, and is associated with disease progression (b= 0.15\, P=0.045).
  Our results significantly advance understanding of disease aetiology and 
 are supporting sensitive diagnostic re-evaluation and targeted laboratory 
 experimentation as well as inclusion criteria for upcoming clinical trials
 .
LOCATION:Seminar Room\, Lab Building East\, ISTA
ORGANIZER:rsix@ist.ac.at
SUMMARY:Roberto Bonelli: Integrative analysis of genomics and metabolomics 
 data elucidate causal mechanism in a rare eye disease
URL:https://talks-calendar.ista.ac.at/events/2016
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