About Cisca Wijmenga

Her work

Cisca Wijmenga (1964) is considered one of the world leaders in the study of the genetics of coeliac disease. Her interdisciplinary research team covers genetics, molecular genetics, epidemiology, immunology, computational biology and bioinformatics. Over the past 15 years, her work has led to a huge advance in the understanding of the disease aetiology, pathology and its genetic basis, and also to models to identify people at risk for developing coeliac disease to allow for prevention and early treatment. She has identified 39 genetic risk loci for coeliac disease and made the important observation that several immune-mediated diseases share part of their genetic basis. This has given the field a strong new impetus, inspiring many projects on other such diseases like rheumatoid arthritis, type 1 diabetes, and Crohn’s disease.

She first postulated the concept of ‘shared genetics for immune-mediated diseases’ in 2005 and was awarded a VICI grant by the Netherlands Organization for Scientific Research (NWO). She has continued to refine this concept and confirmed that celiac disease does indeed share genetic factors with Crohn’s disease, rheumatoid arthritis and type 1 diabetes, presenting the evidence in a highly cited review (Nature Reviews Genetics, 2009). The confirmation of her hypothesis inspired the development of the Immunochip by an international consortium for use in genome-wide association studies. This specific chip is used to screen DNA variants covering all the known immune-related genes. She has performed genome-wide association studies with this chip and they were the first group in the consortium to report their findings (Nature Genetics, 2011).

One of Wijmenga’s strong points is her ability to integrate different types of results and to make good use of bioinformatic techniques. Early on, she was aware of the opportunities that bioinformatics could offer and was able to make it an important part of her research work. This enabled her to construct a human gene network, among other things (Am J Hum Genet, 2006). She is also the principal investigator of a large Top Institute Food and Nutrition (TIFN) program. In 2007 she was instrumental in setting up the Groningen Genomics Coordination Centre, which now supports many departments in the university. It also plays a key role in the analysis and interpretation of the Genome of the Netherlands data (GoNL, see below), a nationwide collaboration led by Wijmenga and in the LifeLines projects.

Her interdisciplinary approach, her unique and large collections of patient materials, her many research partners, and her use of cutting-edge technology mean she is in an excellent position to move beyond gene discovery and translate findings about genetic predisposition into insights on disease mechanisms. She was awarded an ERC advanced grant in 2012 to continue this work.

International visibility & activities

Cisca Wijmenga was trained as a molecular biologist and obtained her PhD cum laude (in 1993) in the field of human genetics. After completing a postdoctoral fellowship under Dr. Francis Collins – at that time the leader of the Human Genome Project – at the US National Human Genome Research Institute (NHGRI), National Institutes of Health (NIH), she started her own research group at Utrecht University. In 2003 she was appointed as a Professor of Human Genetics. In 2007 she was invited to become Professor of Human Genetics at the UMC Groningen and head of the Department of Genetics, which has approximately 250 staff. Wijmenga is internationally oriented and is a visiting scientist for 6 weeks a year at Massachusetts General Hospital and the Broad Institute, in Boston, USA, where she has a long-standing collaboration with Dr. Ramnik Xavier.

In both the Netherlands and the international arena, Wijmenga is greatly respected for her breadth of knowledge and interests, her ready access to an extensive international network, and for being an active and reliable collaborator. Her contribution to science over more than twenty years was recognized in 2012 by her appointment to the Netherlands Royal Academy of Arts and Sciences (KNAW). She is one of only a few female members in the science division in this prestigious Dutch institution. She is also a member of the Royal Holland Society of Sciences and Humanities (Koninklijke Hollandse Maatschappij der Wetenschappen), which was established in 1752. Further examples of her international distinctions include a Fogarty Fellowship to become a postdoctoral fellow at NIH (USA) in 1994, and a Fulbright Scholarship in 2001 to go on a sabbatical to the USA. In 2005 Wijmenga was awarded a prestigious NWO VICI grant and in 2012 an ERC Advanced award. In 2009 she received a Distinguished Visiting Scientist Stipend from the Netherlands Genomics Initiative, and in 2012 a visiting scientist award from the Sigrid Jusélius Foundation (Finland).

Since 2002 she has had 39 PhD students graduate under her supervision, seven of whom were awarded their doctorate degree cum laude. Most of her former PhD students have gone on to pursue a scientific career, either in combination with a medical speciality, or as researchers or postdoctoral fellows; many of them have received major fellowships and awards. She has published >630 articles in peer-reviewed journals, including >55 in Cell, The Lancet, New England Journal of Medicine, and Nature journals (per Jan. 2016, Web of Knowledge h-index 86; GoogleScholar h-index 97; >37,700 citations). Wijmenga’s international reputation is also evident from her frequent invitations to teach abroad and to speak at international meetings. For example, she teaches regularly at the Leena Peltonen School of Human Genomics (Cambridge, UK). She sits on numerous national and international review committees and is often involved in co-organizing international scientific conferences.

See all Wijmenga's publications in GoogleScholar or in PubMed

Systems genetics

Wijmenga's group consists of excellent international researchers with complementary backgrounds in genetics, molecular genetics, epidemiology, immunology, computational biology and bioinformatics. Their integrative approach allows them to connect the knowledge into network models using systems genetics approaches. They have developed a number of innovative tools. They make use of both cell and organism level phenotypes and genomic information, along with non-genetic factors such as the gut microbiome.

Wijmenga's group has recently shown that it is possible to build functional gene networks, expertise that will be crucial for integrating the large datasets in the consortium. They have developed a functional human gene network that integrates information on genes and the functional relationships between genes; it is based on publicly available datasets (http://www.genenetwork.nl). This network was initially developed to associate disease genes with each other. This new tool can assist in pathway analysis; it is a continuation of their original Prioritizer tool and now makes use of gene expression data from 55,000 human, 17,000 mouse and 6,000 rat Affymetrix microarrays from the Gene Expression Omnibus.

The team has also compiled the largest human eQTL dataset (>5,000 samples for which both genome-wide gene expression and genetic data is available). They are often asked to collaborate in large consortia such as GIANT, ENGAGE, and CAGE. Using eQTL mapping, they can now construct regulatory networks in humans. The group is currently generating and integrating multi-omics level data for a large cohort (genetic, epigenetic, transcriptomics, metabolomics, microbiome). They were one of the first to map the genetic determinants that underlie genetic variation at different molecular levels and to integrate information from a broad range of resources.

This work is instrumental in investigating perturbations of molecular networks imposed by many different genetic variants. Wijmenga’s group is now collaborating Prof. Netea's group in Nijmegen; they have combined their expertise in systems genetics and the immunology of infections in a proof-of-principle study, which identified for the first time the transcription signature of fungal sepsis, a severe human infection with 40% mortality (Smeekens et al., Nat Comm, 2013).

At the moment her own research group comprises 5 PhD students, 2 postdocs (one has an NWO VENI fellowship) and 4 young researchers with a tenure-track position (one is an NWO Rubicon fellow, another is a Rosalind Franklin Fellow, and one has both an NGI Horizon Breakthrough grant and an NWO VENI fellowship). The team is supported by 3 technicians and an editor. They often host visiting researchers from her collaborators’ groups and others seeking a sabbatical position, such as Prof. Ramnik Xavier of Harvard Medical School and the Broad Institute, Boston, in the summer of 2013.

The Genome of the Netherlands
Wijmenga is the principal investigator of the Genome of the Netherlands (GoNL, www.nlgenome.nl), which has become a flagship project of BBMRI-NL, greatly contributing to its international visibility due to the scientific interest it has generated. It involves four major population biobanks in the Netherlands, but its data is nationally and internationally accessible in a secure and anonymized way. GoNL has established a map of Dutch genetic variation by the whole genome-sequencing of 250 trio families. This has revealed a large part of the intrinsic genetic variation in the Dutch population. The family-based design offers an excellent opportunity to ascertain alleles and haplotypes accurately and is a valuable resource for extrapolating missing genetic variation (i.e. imputation) in genome-wide association data sets from Dutch cohorts. It can be used to refine association signals and test for association to rare and more population-specific variants (both SNPs and structural variation).

International work visits