Genetics and Genomics of IBD

Inflammatory bowel disease (IBD) involves chronic inflammation of all or part of the digestive tract. IBD primarily includes ulcerative colitis and Crohn’s disease. Familial aggregation and higher concordance rates in monozygotic than dizygotic twins have provided robust evidence for the involvement of genetic factors in the disease etiology. An important epidemiological feature of IBD is that it occurs at significantly different frequencies in different ethnic, demographic and racial groups, and has the highest prevalence among individuals of Ashkenazi Jewish descent.

We are taking advantage of an ongoing recruitment and the world class Division of Gastroenterology at Mount Sinai to conduct genetic, genomic, microbiome, systems biology and functional studies of IBD with the focus on the Ashkenazi Jewish population. We are particularly interested in large families with multiple affected individuals. Our goal is to detect genetic mutations that significantly contribute to the development of IBD and functionally validate them. This knowledge of the genetic risk may help identify individuals at high risk of developing the disease and discover new pharmaceutical targets to prevent, postpone and/or treat IBD.

Systems Biology Approach to IBD

Next-generation technologies that measure biological parameters on a genome-wide scale (“omics” data) are continuously being refined and offered at ever-decreasing costs. Nevertheless, our understanding of disease is still limited because the susceptibility loci do not necessarily inform on how the biological processes cause a disease. Networks can be inferred from various kinds of “omic” datasets with the use of computational inference algorithms. We are capitalizing on the strengths of the SHARE consortium, The Sinai-Helmsley Alliance for Research Excellence (SHARE), a collaboration of seven academic research medical centers across the country, aspires to improve the lives of patients with Crohn’s disease and ulcerative colitis through cutting edge biomedical research, that includes ongoing recruitment of the large IBD patient population.

With the state-of-the-art facilities, as well as world-class expertise in probabilistic causal models integrating high-dimensional, large-scale “omics” data, our goal is to identify novel genes, pathways, and networks associated with IBD, ultimately resulting in the identification of the best targets for improved diagnostics and therapeutics using systems biology tools.


IBD affects women during their reproductive years and 25% become pregnant after an initial diagnosis. Accumulating evidence suggests that newborn babies are not microbe-free and the types of bacteria found in their first stool, also known as meconium, have been linked to maternal diseases, including diabetes and eczema. The source of these microbes is of continued interest, because the initial colonization of bacteria is believed to play a crucial role in the development of the infant’s immune system and consequently the protection against the risk of diseases later in life.

The MECONIUM (Exploring MEChanisms Of disease traNsmission IUtero through the Microbiome) study is aimed to compare the bacterial profiles of women with and without IBD during pregnancy and identify bacteria passed from mothers with IBD. Moreover, the goal is to explore the role of genetic make-up, disease activity throughout pregnancy, medications and clinical features on the bacterial composition of the baby. In addition, we will assess if feeding behavior (breastfeeding versus formula) and/or antibiotic use early in life help modify the microbiome. Given that the maternal gut bacteria can be manipulated by diet, food supplementation, and other ways, our study can help identify the types of bacteria that need to be altered prior or during pregnancy to significantly reduce the IBD risk transmission.

Cardiovascular Disease

With over a third of persons living with HIV (PLWH) being over 50 and cardiovascular disease (CVD) occurring at a higher rate in PLWH, we are likely to witness a dramatic rise in the incidence of CVD in this population over the next decade. The underlying pathogenesis of cardiometabolic complications in PLWH has not yet been fully elucidated with the unique risk factors only partially accounting for increased CVD-related risks among PLWH. In recent years, there has been rapid growth in understanding the genetic basis for CVD in the general population; however, there is very limited data related to the impact of genetics on CVD in PLWH. The goal of this study is to assess if the genetic risk burden can help explain a higher risk of CVD in PLWH with exposure to antiretroviral therapy and identify therapeutic opportunities to mitigate CVD-related complications using the shared HIV/CVD molecular networks.

Craniosynostosis Network

Craniosynostosis is a common malformation occurring in ~4 per 10,000 live births in which the sutures close too early, causing long-term complications for normal brain and skull growth. Most often, craniosynostosis appears as an isolated, nonsyndromic, anomaly. Unilateral or bilateral fusion of the coronal suture accounts for 20–30% of all nonsyndromic craniosynostosis cases. The etiology of nonsyndromic coronal craniosynostosis is not well understood, although the published literature suggests that it is a multifactorial condition. About 5–14% of coronal craniosynostosis patients have a positive family history, with a specific genetic etiology identified in >25% of nonsyndromic coronal craniosynostosis cases. Yet, the other causes for nonsyndromic craniosynostosis and its phenotypic heterogeneity remain largely unknown. In the first and only genome-wide association study of nonsyndromic craniosynostosis our group identified two regions, downstream of BMP2 gene and within BBS9 gene, associated with a 4-5 fold increased risk of sagittal nonsyndromic craniosynostosis. Although BMP2 and BBS9 are genes with a role in skeletal development, there are several genes that are yet to be identified.

Given that the phenotypic characterization of nonsyndromic coronal craniosynostosis is incomplete and that its causes remain largely unknown, the objective of Craniosynostosis Network is to identify and functionally validate genes and biological pathways contributing to common forms of nonsyndromic coronal craniosynostosis and to the related continuum of craniofacial phenotypes.

Learn more: Craniosynostosis Network     What is Craniosynostosis?     Network Organization     Network Directory

Frequently Asked Questions (FAQs)    Publications    Enroll