News

Familial hypercholesterolemia (FH) is an oligogenic disorder characterized by markedly elevated low-density lipoprotein cholesterol (LDLC) levels.
As FH increases the risk for coronary artery disease (CAD) and myocardial infarction (MI), it might be specifically overlooked in the large number of such patients.
Here, Ingrid Brænne et al. systematically examined the frequency of potential FH-causing variants by exome sequencing in 255 German patients with premature MI and a positive family history for CAD. Our data reveal that a large proportion of FH patients indeed escape the diagnosis, even when they have premature MI.
Hence, systematic molecular-genetic screening for FH in such patients may reveal a substantial number of cases and thereby allow a timely LDLC-lowering in both FH/MI patients as well as their variant carrying family members.
In conclusion, our work demonstrates that exome sequencing can be used for FH-variant screening.
As the sequencing costs have decreased dramatically, exome sequencing might become the method of choice for molecular genetic screening of, for instance, FH.

Further information:
http://www.nature.com/ejhg/journal/vaop/ncurrent/abs/ejhg2015100a.html

The BMBF funded consortium e:AtheroSysMed has met for two days in Aying nearby Munich to kick-off the project.
The consortium brings together major national and international resources and scientists from a wide spectrum of disciplines (e.g. clinicians, geneticists, epidemiologists, systems biologists, bioinformaticians, mathematicians). 30 participants – from senior scientists to PhD students – discussed project ideas and work plans for the next three years. Besides discussing science this meeting was also meant to get to know each other better.
The goal of the consortium is to better understand the genetics of atherosclerosis and stroke by identifying and investigating functional pathways.

Today the DFG informed us that the Clinical Research Unit 303 „Pemphigoid Diseases“ gets funded for at least three years with an option for three additional years. This CRC will be coordinated by Detlef Zillikens and Christian Sadik from the Dermatology department. The IIEG is, together with Inke König,  involved in a Z-project – Biostatistics and Systems Medicine Core Unit.

Pemphigoid diseases (PD) are a group of subepidermal autoimmune blistering skin diseases. The epidemiology and pathogenesis of PD is not entirely clear. This CRC aims to unravel the pathomechanism of this threatening disease.

Jeanette Erdmann is now part of the Frontiers Community as an Associate Editor of Cardiovascular Genetics (specialty section of Frontiers in Cardiovascular Medicine) a very new, global and peer-reviewed Open Access medical journal providing unrestricted, online access to publications on diagnostic and therapeutic advances in cardiology and cardiovascular disease.

The specialty section Cardiovascular Genetics is devoted to studies enhancing our understanding of the genetic and epigenetic causes of cardiovascular diseases in order to better understand disease development and progression.

With this aim the journal fits extremely well to the IIEG and its members.

Link: http://www.frontiersin.org/Cardiovascular_Genetics/about

Based on extensive genotypic data from CARDIoGRAM we started a large-scale integrative genomic analyses together with colleagues from USA, Australia, Canada, UK, Singapore, and Germany.

More precisely, we conducted an analysis where we used the information of gene-gene interactions to capture groups of genes that are most likely to increase heart disease risk. In the end, we not only confirmed the importance of several known CAD risk processes such as the metabolism and transport of cholesterol, immune response, and blood coagulation, but also revealed many novel processes such as neuroprotection, cell cycle, and proteolysis that were not previously implicated in CAD. These results published in PLOS Genetics highlight the value of integrating population genetic data with diverse resources that functionally annotate the human genome.

Link: http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1004502

The institute is seeking for a highly motivated PhD student and/or PostDoc for genetic epidemiology.

The institute is seeking for highly motivated PhD students and/or PostDocs for genetic epidemiology and cell biology to study the function of recently identified CAD risk genes in either mice, zebrafish and/or human cells.

On behalf of the e:Med Project Committee we kindly invite you to attend the e:Med Meeting 2015 on Systems Medicine, October 26 – 28 at the DKFZ in Heidelberg.

Please find further information and forms for Registration and Abstract Submission at
http://www.sys-med.de/de/meeting.
Take this chance to meet your colleagues.

There will be no conference fee, but Registration is mandatory.

Abstract submission will be open till September 6, 2015.
The preliminary program comprises five symposia:

1) Epigenetic Methods
2) Genome Editing
3) Cardiovascular Disease
4) Computational Approaches & Clinical Utilities
5) Cancer

Unveil your work to the community by submitting an abstract for talk or poster on the session topics. Six talks will be chosen for presentation in Short Talks. Your Poster will be on display at the poster exposition throughout the conference.
We are looking forward to welcoming you in Heidelberg.
Your e:Med Management Office

In close collaboration with several national and international colleagues members of the IIEG conducted large-scale exome-sequencing in thousands of patients with coronary artery disease and healthy controls. Three papers have been published in the last three months in the prestigious journals NEJM and Nature.

First, we reported that rare mutations disrupting APOC3 function were associated with lower levels of plasma triglycerides and APOC3. Carriers of these mutations were found to have a reduced risk of coronary heart disease.

Second, we described naturally occurring rare loss-of-function mutations in NPC1L1, a drug target for lowering LDL-cholesterol, which were found to be associated with reduced plasma LDL cholesterol levels and a reduced risk of coronary heart disease. Interestingly, human mutations that inactivate a gene encoding a drug target can mimic the action of an inhibitory drug and thus can be used to infer potential effects of that drug.

Third, we identified rare mutations in APOA5 gene which confer a more than two-fold risk for myocardial infarction.

http://www.nejm.org/doi/full/10.1056/NEJMoa1307095

http://www.nejm.org/doi/full/10.1056/NEJMoa1405386

http://www.nature.com/nature/journal/vaop/ncurrent/full/nature13917.html

Since February 2015 the Medizinische Klinik II (director: Prof. Holger Thiele), the Klinik für Herz- und thorakale Gefäßchirurgie
(director: Prof. Hans-H. Sievers), and the Institut für Integrative und Experimentelle Genomik (IIEG) (director: Prof. Jeanette Erdmann) are united under one roof as the „Universitäres Herzzentrum Lübeck“ (UHZL).

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This new foundation will enable closer collaborations not only between the clinicians but also between the clinicians and the research groups at the IIEG. Such very close collaborations are neccessary for translational research from bench to bedside.
In February 2016 a Symposium will be organized to introduce and celebrate the UHZL.

More infos about the Symposium will follow soon.