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Article ; Online: From LD-based mapping to GWAS.

Wijmenga, Cisca

2021 Volume 22, Issue 8, Page(s) 480–481

MeSH term(s)	Genome-Wide Association Study ; Humans ; Linkage Disequilibrium
Language	English
Publishing date	2021-04-21
Publishing country	England
Document type	Journal Article
ZDB-ID	2035157-4
ISSN	1471-0064 ; 1471-0056
ISSN (online)	1471-0064
ISSN	1471-0056
DOI	10.1038/s41576-021-00366-4
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Zs.A 5474: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 40: Show issues

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Book: Germs, genes, and host defense

Wijmenga, Cisca

(NIH Wednesday afternoon lecture)

2016

Abstract: CIT): Wednesday Afternoon Lecture Series The Human Functional Genomics Project (HFGP) is a large-scale project that aims to identify the consequences that genetic variation in human DNA and the complex colonization with microbial communities ( ... ...

Institution	National Institutes of Health (U.S.),
Author's details	Cisca Wijmenga
Series title	NIH Wednesday afternoon lecture
Abstract	(CIT): Wednesday Afternoon Lecture Series The Human Functional Genomics Project (HFGP) is a large-scale project that aims to identify the consequences that genetic variation in human DNA and the complex colonization with microbial communities (microbiome) have on the physiological processes in the human body, with a special focus on the immune system in health and human diseases. HFGP includes different deeply phenotyped cohorts with multi-omics information such as transcriptional profiling, gut microbiota composition and extensive immune phenotyping. For her lecture, Dr. Wijmenga will describe the potential of studying variation in the general population and the opportunities for translational research. She will also show how to make use of the LifeLines-deep cohort to establish what constitutes a "normal" gut microbiome and to show how microbiota composition correlates with a range of factors including diet, use of medication, and genetic factors. Her laboratory uses the 500 functional genomics (500FG) cohort to further characterize the interaction between the genetic background of the host, the gut microbiome composition, and the immune response against important human pathogens. The information from both LifeLines-deep and 500FG is subsequently used to identify genes that underlie the genetic susceptibility to systemic candida infections.
MeSH term(s)	Gastrointestinal Microbiome/genetics ; Gastrointestinal Tract ; Cytokines/genetics ; Candidemia/genetics
Language	English
Size	1 online resource (1 streaming video file (59 min.)) :, color, sound.
Document type	Book
Note	Closed-captioned.
Database	Catalogue of the US National Library of Medicine (NLM)

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Article ; Online: The importance of cohort studies in the post-GWAS era.

Wijmenga, Cisca / Zhernakova, Alexandra

Nature genetics

2018 Volume 50, Issue 3, Page(s) 322–328

Abstract: The past decade has seen enormous success of wide-scale genetic studies in identifying genetic variants that modify individuals' predisposition to common diseases. However, the interpretation and functional understanding of these variants lag far behind. ...

Abstract	The past decade has seen enormous success of wide-scale genetic studies in identifying genetic variants that modify individuals' predisposition to common diseases. However, the interpretation and functional understanding of these variants lag far behind. In this Perspective, we discuss opportunities for using large-scale cohort studies to investigate the downstream molecular effects of SNPs at different 'omics' data levels. We point to the pivotal role of population cohorts in establishing causality and advancing drug discovery. In particular, we focus on the breadth-versus-depth concepts of population studies, on data harmonization, and on the challenges, ethical aspects and future perspectives of cohort studies.
MeSH term(s)	Cohort Studies ; Diet Surveys ; Epidemiologic Research Design ; Female ; Gastrointestinal Microbiome/physiology ; Gene-Environment Interaction ; Genetic Predisposition to Disease ; Genetic Variation ; Genetics, Population/methods ; Genetics, Population/trends ; Genome-Wide Association Study/methods ; Genome-Wide Association Study/statistics & numerical data ; Genome-Wide Association Study/trends ; History, 20th Century ; History, 21st Century ; Humans ; Infant, Newborn ; Male ; Parturition ; Polymorphism, Single Nucleotide ; Population Dynamics
Language	English
Publishing date	2018-03-06
Publishing country	United States
Document type	Historical Article ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1108734-1
ISSN	1546-1718 ; 1061-4036
ISSN (online)	1546-1718
ISSN	1061-4036
DOI	10.1038/s41588-018-0066-3
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Zs.A 3613: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 46: Show issues

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Article ; Online: Context-specific effects of genetic variants associated with autoimmune disease.

Jonkers, Iris H / Wijmenga, Cisca

Human molecular genetics

2017 Volume 26, Issue R2, Page(s) R185–R192

Abstract: Autoimmune diseases such as rheumatoid arthritis and coeliac disease are typical examples of complex genetic diseases caused by a combination of genetic and non-genetic risk factors. Insight into the genetic risk factors (single nucleotide polymorphisms ( ...

Abstract	Autoimmune diseases such as rheumatoid arthritis and coeliac disease are typical examples of complex genetic diseases caused by a combination of genetic and non-genetic risk factors. Insight into the genetic risk factors (single nucleotide polymorphisms (SNPs)) has increased since genome-wide association studies (GWAS) became possible in 2007 and, for individual diseases, SNPs can now explain some 15-50% of genetic risk. GWAS have also shown that some 50% of the genetic risk factors for individual autoimmune diseases overlap between different diseases. Thus, shared risk factors may converge to pathways that, when perturbed by genetic variation, predispose to autoimmunity in general. This raises the question of what determines disease specificity, and suggests that identical risk factors may have different effects in various autoimmune diseases. Addressing this question requires translation of genetic risk factors to causal genes and then to molecular and cellular pathways. Since >90% of the genetic risk factors are found in the non-coding part of the genome (i.e. outside the exons of protein-coding genes) and can have an impact on gene regulation, there is an urgent need to better understand the non-coding part of the genome. Here, we will outline the methods being used to unravel the gene regulatory networks perturbed in autoimmune diseases and the importance of doing this in the relevant cell types. We will highlight findings in coeliac disease, which manifests in the small intestine, to demonstrate how cell type and disease context can impact on the consequences of genetic risk factors.
MeSH term(s)	Arthritis, Rheumatoid/genetics ; Arthritis, Rheumatoid/immunology ; Autoimmune Diseases/etiology ; Autoimmune Diseases/genetics ; Autoimmunity/genetics ; Autoimmunity/immunology ; Gene Expression Regulation/genetics ; Gene Regulatory Networks/genetics ; Gene Regulatory Networks/immunology ; Genetic Predisposition to Disease ; Genetic Variation/genetics ; Genome-Wide Association Study ; Genotype ; Humans ; Polymorphism, Single Nucleotide/genetics ; Quantitative Trait Loci ; Risk Factors
Language	English
Publishing date	2017-05-15
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	1108742-0
ISSN	1460-2083 ; 0964-6906
ISSN (online)	1460-2083
ISSN	0964-6906
DOI	10.1093/hmg/ddx254
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Zs.A 3469: Show issues

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Article: Celiac disease-on-chip: Modeling a multifactorial disease in vitro.

Moerkens, Renée / Mooiweer, Joram / Withoff, Sebo / Wijmenga, Cisca

United European gastroenterology journal

2019 Volume 7, Issue 4, Page(s) 467–476

Abstract: Conventional model systems cannot fully recapitulate the multifactorial character of complex diseases like celiac disease (CeD), a common chronic intestinal disorder in which many different genetic risk factors interact with environmental factors such as ...

Abstract	Conventional model systems cannot fully recapitulate the multifactorial character of complex diseases like celiac disease (CeD), a common chronic intestinal disorder in which many different genetic risk factors interact with environmental factors such as dietary gluten. However, by combining recently developed human induced pluripotent stem cell (hiPSC) technology and organ-on-chip technology, in vitro intestine-on-chip systems can now be developed that integrate the genetic background of complex diseases, the different interacting cell types involved in disease pathology, and the modulating environmental factors such as gluten and the gut microbiome. The hiPSCs that are the basis of these systems can be generated from both diseased and healthy individuals, which means they can be stratified based on their load of genetic risk factors. A CeD-on-chip model system has great potential to improve our understanding of disease etiology and accelerate the development of novel treatments and preventive therapies in CeD and other complex diseases.
MeSH term(s)	Celiac Disease/etiology ; Celiac Disease/physiopathology ; Cell Communication/physiology ; Genetic Predisposition to Disease ; Glutens/immunology ; Humans ; Induced Pluripotent Stem Cells/physiology ; Intestinal Mucosa/cytology ; Intestinal Mucosa/physiopathology ; Lab-On-A-Chip Devices ; Risk Factors
Chemical Substances	Glutens (8002-80-0)
Language	English
Publishing date	2019-03-14
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2728585-6
ISSN	2050-6414 ; 2050-6406
ISSN (online)	2050-6414
ISSN	2050-6406
DOI	10.1177/2050640619836057
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Coeliac disease and autoimmune disease-genetic overlap and screening.

Lundin, Knut E A / Wijmenga, Cisca

Nature reviews. Gastroenterology & hepatology

2015 Volume 12, Issue 9, Page(s) 507–515

Abstract: Coeliac disease is a treatable, gluten-induced disease that often occurs concurrently with other autoimmune diseases. In genetic studies since 2007, a partial genetic overlap between these diseases has been revealed and further insights into the ... ...

Abstract	Coeliac disease is a treatable, gluten-induced disease that often occurs concurrently with other autoimmune diseases. In genetic studies since 2007, a partial genetic overlap between these diseases has been revealed and further insights into the pathophysiology of coeliac disease and autoimmunity have been gained. However, genetic screening is not sensitive and specific enough to accurately predict disease development. The current method to diagnose individuals with coeliac disease is serological testing for the presence of autoantibodies whilst the patient is on a regular, gluten-containing diet, followed by gastroduodenoscopy with duodenal biopsy. Serological test results can also predict the probability of coeliac disease development, even if asymptomatic. In patients with autoimmune diseases known to occur alongside coeliac disease (particularly type 1 diabetes mellitus or thyroid disorders), disease screening-and subsequent treatment if coeliac disease is detected-could have beneficial effects on progression or potential complications of both diseases, owing to the effectiveness of gluten-free dietary interventions in coeliac disease. However, whether diagnosis of coeliac disease and subsequent dietary treatment can prevent autoimmune diseases is debated. In this Review, the genetic and immunological features of coeliac disease, overlap with other autoimmune diseases and implications for current screening strategies will be discussed.
MeSH term(s)	Autoimmune Diseases/complications ; Celiac Disease/diagnosis ; Celiac Disease/genetics ; Celiac Disease/immunology ; Celiac Disease/therapy ; Genetic Testing ; Humans
Language	English
Publishing date	2015-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2493722-8
ISSN	1759-5053 ; 1759-5045
ISSN (online)	1759-5053
ISSN	1759-5045
DOI	10.1038/nrgastro.2015.136
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Zs.A 6020: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MG 97: Show issues

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Article ; Online: Celiac disease genetics: past, present and future challenges.

Wijmenga, Cisca / Gutierrez-Achury, Javier

Journal of pediatric gastroenterology and nutrition

2014 Volume 59 Suppl 1, Page(s) S4–7

Abstract: In the past few years there has been enormous progress in unraveling the genetic basis of celiac disease (CD). Apart from the well-known association to HLA, there are currently 40 genomic loci associated to CD. Most of these loci show pleiotropic effects ...

Abstract	In the past few years there has been enormous progress in unraveling the genetic basis of celiac disease (CD). Apart from the well-known association to HLA, there are currently 40 genomic loci associated to CD. Most of these loci show pleiotropic effects across many autoimmune diseases and highlight the importance of a dysregulated immune system in the predisposition to CD. It is still too early, however, to use genetics in clinical practice for predicting individual risk. The major challenge for the future is to translate genetic findings into a better understanding of the underlying disease mechanism and to design new ways to treat CD and prevent its development.
MeSH term(s)	Autoimmune Diseases/genetics ; Celiac Disease/genetics ; Celiac Disease/immunology ; Genetic Loci ; Genetic Pleiotropy ; Genetic Predisposition to Disease ; HLA Antigens/genetics ; Humans ; Risk Factors
Chemical Substances	HLA Antigens
Language	English
Publishing date	2014-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	603201-1
ISSN	1536-4801 ; 0277-2116
ISSN (online)	1536-4801
ISSN	0277-2116
DOI	10.1097/01.mpg.0000450392.23156.10
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Zs.A 1728: Show issues

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Article ; Online: Systematic review with meta-analysis: the risks of proton pump inhibitors during pregnancy.

Li, Cheng Mei / Zhernakova, Alexandra / Engstrand, Lars / Wijmenga, Cisca / Brusselaers, Nele

Alimentary pharmacology & therapeutics

2020 Volume 51, Issue 4, Page(s) 410–420

Abstract: Background: There have been safety concerns considering long-term proton pump inhibitor (PPI) use, also during pregnancy.: Aims: To assess the risk of adverse neonatal outcomes associated with maternal intake of PPIs by means of systematic review and ...

Abstract	Background: There have been safety concerns considering long-term proton pump inhibitor (PPI) use, also during pregnancy. Aims: To assess the risk of adverse neonatal outcomes associated with maternal intake of PPIs by means of systematic review and meta-analysis. Methods: The systematic search included PubMed, Web of Science, Cochrane Database and Embase (inception until June 2019). All studies reporting ≥1 adverse pregnancy outcome comparing PPI users to non-users. Histamine-2 receptor antagonists (H2RA) were also compared to both non-users and PPI users. Outcomes included congenital malformations, abortion, stillbirth, neonatal death, preterm birth, small for gestational age and low birth weight. Pooled odds ratios (OR) and 95% confidence intervals (CI) were obtained by random-effects modelling. PROSPERO study-protocol: CRD42018103320. Results: In total, 26 observational studies (20 cohort, 6 case-control studies) were identified, of which 19 assessed PPIs and 12 H2RA. PPI use was associated with an increased risk of congenital malformations (OR 1.28, 95% CI 1.09-1.52), especially in case-control studies (OR 2.04, 1.46-2.86). No associations were found between H2RA and congenital malformations. No significant associations were found between PPI use and abortions, stillbirth, neonatal death, preterm birth and low-birth weight, although H2RA use may be associated with an increased risk of preterm birth (OR 1.25, 95% CI 1.02-1.56). Although statistical heterogeneity and the risk of bias were overall low, clinical heterogeneity, information and selection bias may be present in the individual studies. Conclusions: This meta-analysis suggests an association between maternal PPI use and congenital malformations in humans, yet power was insufficient to assess specific malformations and drugs.
MeSH term(s)	Abnormalities, Drug-Induced/epidemiology ; Case-Control Studies ; Cohort Studies ; Congenital Abnormalities/epidemiology ; Female ; Heartburn/drug therapy ; Heartburn/epidemiology ; Histamine H2 Antagonists/adverse effects ; Humans ; Infant, Low Birth Weight ; Infant, Newborn ; Infant, Small for Gestational Age ; Male ; Pregnancy ; Pregnancy Complications/drug therapy ; Pregnancy Complications/epidemiology ; Pregnancy Outcome/epidemiology ; Premature Birth/epidemiology ; Proton Pump Inhibitors/adverse effects ; Risk Factors ; Stillbirth/epidemiology
Chemical Substances	Histamine H2 Antagonists ; Proton Pump Inhibitors
Language	English
Publishing date	2020-01-07
Publishing country	England
Document type	Journal Article ; Meta-Analysis ; Systematic Review
ZDB-ID	639012-2
ISSN	1365-2036 ; 0269-2813 ; 0953-0673
ISSN (online)	1365-2036
ISSN	0269-2813 ; 0953-0673
DOI	10.1111/apt.15610
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Zs.A 2206: Show issues

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Article ; Online: Non-classical clinical presentation at diagnosis by male celiac disease patients of older age.

Tan, Ineke L / Withoff, Sebo / Kolkman, Jeroen J / Wijmenga, Cisca / Weersma, Rinse K / Visschedijk, Marijn C

European journal of internal medicine

2020 Volume 83, Page(s) 28–33

Abstract: Background: . In a biopsy-proven adult celiac disease (CeD) cohort from the Netherlands, male patients were diagnosed with CeD at significantly older ages than female patients.: Objectives: To identify which factors contribute to diagnosis later in ... ...

Abstract	Background: . In a biopsy-proven adult celiac disease (CeD) cohort from the Netherlands, male patients were diagnosed with CeD at significantly older ages than female patients. Objectives: To identify which factors contribute to diagnosis later in life and whether diagnostic delay influences improvement of symptoms after starting a gluten-free diet (GFD). Methods: . We performed a questionnaire study in 211 CeD patients (67:144, male:female) with median age at diagnosis of 41.8 years (interquartile range: 25-58) and at least Marsh 2 histology. Results: . Classical symptoms (diarrhea, fatigue, abdominal pain and/or weight loss) were more frequent in women than men, but sex was not significantly associated with age at diagnosis. In a multivariate analysis, a non-classical presentation (without any classical symptoms) and a negative family history of CeD were significant predictors of older age at diagnosis (coefficients of 8 and 12 years, respectively). A delay of >3 years between first symptom and diagnosis was associated with slower improvement of symptoms after start of GFD, but not with sex, presentation of classical symptoms or age at diagnosis. Conclusion: . Non-classical CeD presentation is more prevalent in men and is associated with a diagnosis of CeD later in life. Recognizing CeD sooner after onset of symptoms is important because a long diagnostic delay is associated with a slower improvement of symptoms after starting a GFD.
MeSH term(s)	Adult ; Aged ; Celiac Disease/diagnosis ; Celiac Disease/epidemiology ; Delayed Diagnosis ; Diarrhea/etiology ; Diet, Gluten-Free ; Female ; Humans ; Male ; Middle Aged ; Netherlands/epidemiology
Language	English
Publishing date	2020-11-17
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1038679-8
ISSN	1879-0828 ; 0953-6205
ISSN (online)	1879-0828
ISSN	0953-6205
DOI	10.1016/j.ejim.2020.09.020
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Zs.A 2608: Show issues

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Article ; Online: Host Genetics and Gut Microbiome: Challenges and Perspectives.

Kurilshikov, Alexander / Wijmenga, Cisca / Fu, Jingyuan / Zhernakova, Alexandra

Trends in immunology

2017 Volume 38, Issue 9, Page(s) 633–647

Abstract: The mammalian gut is colonized by trillions of microorganisms collectively called the microbiome. It is increasingly clear that this microbiome has a critical role of in many aspects of health including metabolism and immunity. While environmental ... ...

Abstract	The mammalian gut is colonized by trillions of microorganisms collectively called the microbiome. It is increasingly clear that this microbiome has a critical role of in many aspects of health including metabolism and immunity. While environmental factors such as diet and medications have been shown to influence the microbiome composition, the role of host genetics has only recently emerged in human studies and animal models. In this review, we summarize the current state of microbiome research with an emphasis on the effect of host genetics on the gut microbiome composition. We focus particularly on genetic determinants of the host immune system that help shape the gut microbiome and discuss avenues for future research.
Language	English
Publishing date	2017-09
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2036831-8
ISSN	1471-4981 ; 1471-4906
ISSN (online)	1471-4981
ISSN	1471-4906
DOI	10.1016/j.it.2017.06.003
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Zs.MG 2: Show issues

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