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2. Whole-genome sequencing of African Americans implicates differential genetic architecture in inflammatory bowel disease.

Author

Somineni, Hari, Nagpal, Sini, Venkateswaran, Suresh, Cutler, David, Okou, David, Haritunians, Talin, Simpson, Claire, Begum, Ferdouse, Datta, Lisa, Quiros, Antonio, Seminerio, Jenifer, Mengesha, Emebet, Alexander, Jonathan, Baldassano, Robert, Dudley-Brown, Sharon, Cross, Raymond, Dassopoulos, Themistocles, Denson, Lee, Dhere, Tanvi, Iskandar, Heba, Dryden, Gerald, Hou, Jason, Hussain, Sunny, Hyams, Jeffrey, Isaacs, Kim, Kader, Howard, Kappelman, Michael, Katz, Jeffry, Kellermayer, Richard, Kuemmerle, John, Lazarev, Mark, Li, Ellen, Mannon, Peter, Moulton, Dedrick, Newberry, Rodney, Patel, Ashish, Pekow, Joel, Saeed, Shehzad, Valentine, John, Wang, Ming-Hsi, McCauley, Jacob, Abreu, Maria, Jester, Traci, Molle-Rios, Zarela, Palle, Sirish, Scherl, Ellen, Kwon, John, Rioux, John, Duerr, Richard, Silverberg, Mark, Zwick, Michael, Stevens, Christine, Daly, Mark, Cho, Judy, Gibson, Greg, McGovern, Dermot, Brant, Steven, and Kugathasan, Subra

Subjects
CALB2, PTGER4, differential genetic architecture, polygenic risk scores, rare variants, trans-ethnic comparative analysis, understudied populations, whole-genome sequencing of African Americans, Black or African American, Aged, Aged, 80 and over, Calbindin 2, Colitis, Ulcerative, Crohn Disease, Female, Gene Frequency, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Inflammatory Bowel Diseases, Male, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Receptors, Prostaglandin E, EP4 Subtype, White People, Whole Genome Sequencing
Abstract

Whether or not populations diverge with respect to the genetic contribution to risk of specific complex diseases is relevant to understanding the evolution of susceptibility and origins of health disparities. Here, we describe a large-scale whole-genome sequencing study of inflammatory bowel disease encompassing 1,774 affected individuals and 1,644 healthy control Americans with African ancestry (African Americans). Although no new loci for inflammatory bowel disease are discovered at genome-wide significance levels, we identify numerous instances of differential effect sizes in combination with divergent allele frequencies. For example, the major effect at PTGER4 fine maps to a single credible interval of 22 SNPs corresponding to one of four independent associations at the locus in European ancestry individuals but with an elevated odds ratio for Crohn disease in African Americans. A rare variant aggregate analysis implicates Ca2+-binding neuro-immunomodulator CALB2 in ulcerative colitis. Highly significant overall overlap of common variant risk for inflammatory bowel disease susceptibility between individuals with African and European ancestries was observed, with 41 of 241 previously known lead variants replicated and overall correlations in effect sizes of 0.68 for combined inflammatory bowel disease. Nevertheless, subtle differences influence the performance of polygenic risk scores, and we show that ancestry-appropriate weights significantly improve polygenic prediction in the highest percentiles of risk. The median amount of variance explained per locus remains the same in African and European cohorts, providing evidence for compensation of effect sizes as allele frequencies diverge, as expected under a highly polygenic model of disease.

Published
2021

3. Fecal microbiota transplantation for the treatment of recurrent and severe Clostridium difficile infection in solid organ transplant recipients: A multicenter experience

Author

Cheng, Yao-Wen, Phelps, Emmalee, Ganapini, Vincent, Khan, Noor, Ouyang, Fangqian, Xu, Huiping, Khanna, Sahil, Tariq, Raseen, Friedman-Moraco, Rachel J, Woodworth, Michael H, Dhere, Tanvi, Kraft, Colleen S, Kao, Dina, Smith, Justin, Le, Lien, El-Nachef, Najwa, Kaur, Nirmal, Kowsika, Sree, Ehrlich, Adam, Smith, Michael, Safdar, Nasia, Misch, Elizabeth Ann, Allegretti, Jessica R, Flynn, Ann, Kassam, Zain, Sharfuddin, Asif, Vuppalanchi, Raj, and Fischer, Monika

Subjects
Clinical Research, Transplantation, Vaccine Related, Biodefense, Prevention, Emerging Infectious Diseases, Infectious Diseases, Organ Transplantation, Patient Safety, Digestive Diseases, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Infection, Clostridioides difficile, Clostridium Infections, Fecal Microbiota Transplantation, Female, Follow-Up Studies, Humans, Incidence, Male, Middle Aged, Recurrence, Retrospective Studies, Transplant Recipients, Treatment Outcome, United States, clinical research, practice, complication: infectious, immunosuppression, immune modulation, infection and infectious agents - bacterial: Clostridium difficile, infectious disease, intestinal disease: infectious, organ transplantation in general, patient safety, clinical research/practice, immunosuppression/immune modulation, Medical and Health Sciences, Surgery
Abstract

Fecal microbiota transplant (FMT) is recommended for Clostridium difficile infection (CDI) treatment; however, use in solid organ transplantation (SOT) patients has theoretical safety concerns. This multicenter, retrospective study evaluated FMT safety, effectiveness, and risk factors for failure in SOT patients. Primary cure and overall cure were defined as resolution of diarrhea or negative C difficile stool test after a single FMT or after subsequent FMT(s) ± anti-CDI antibiotics, respectively. Ninety-four SOT patients underwent FMT, 78% for recurrent CDI and 22% for severe or fulminant CDI. FMT-related adverse events (AE) occurred in 22.3% of cases, mainly comprising self-limiting conditions including nausea, abdominal pain, and FMT-related diarrhea. Severe AEs occurred in 3.2% of cases, with no FMT-related bacteremia. After FMT, 25% of patients with underlying inflammatory bowel disease had worsening disease activity, while 14% of cytomegalovirus-seropositive patients had reactivation. At 3 months, primary cure was 58.7%, while overall cure was 91.3%. Predictors of failing a single FMT included inpatient status, severe and fulminant CDI, presence of pseudomembranous colitis, and use of non-CDI antibiotics at the time of FMT. These data suggest FMT is safe in SOT patients. However, repeated FMT(s) or additional antibiotics may be needed to optimize rates of cure with FMT.

Published
2019

4. Fecal Microbiota Transplantation Is Safe and Effective in Patients With Clostridioides difficile Infection and Cirrhosis

Author

Cheng, Yao-Wen, Alhaffar, Dana, Saha, Srishti, Khanna, Sahil, Bohm, Matthew, Phelps, Emmalee, Ghabril, Marwan, Orman, Eric, Sashidhar, Sagi, Rogers, Nicholas, Xu, Huiping, Khoruts, Alexander, Vaughn, Byron, Kao, Dina, Wong, Karen, Cammarota, Giovanni, Ianiro, Gianluca, Dhere, Tanvi, Kraft, Colleen S., Mehta, Nirja, Woodworth, Michael H., Allegretti, Jessica R., Nativ, Lotem, Marcus, Jenna, El-Nachef, Najwa, and Fischer, Monika

Published
2021
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5. Genome-Wide Association Study Identifies African-Specific Susceptibility Loci in African Americans With Inflammatory Bowel Disease.

Author

Brant, Steven, Okou, David, Simpson, Claire, Cutler, David, Haritunians, Talin, Bradfield, Jonathan, Chopra, Pankaj, Prince, Jarod, Begum, Ferdouse, Kumar, Archana, Huang, Chengrui, Venkateswaran, Suresh, Datta, Lisa, Wei, Zhi, Thomas, Kelly, Herrinton, Lisa, Klapproth, Jan-Micheal, Quiros, Antonio, Seminerio, Jenifer, Liu, Zhenqiu, Alexander, Jonathan, Baldassano, Robert, Dudley-Brown, Sharon, Cross, Raymond, Dassopoulos, Themistocles, Denson, Lee, Dhere, Tanvi, Dryden, Gerald, Hanson, John, Hou, Jason, Hussain, Sunny, Hyams, Jeffrey, Isaacs, Kim, Kader, Howard, Kappelman, Michael, Katz, Jeffry, Kellermayer, Richard, Kirschner, Barbara, Kuemmerle, John, Kwon, John, Lazarev, Mark, Li, Ellen, Mack, David, Mannon, Peter, Moulton, Dedrick, Newberry, Rodney, Osuntokun, Bankole, Patel, Ashish, Saeed, Shehzad, Targan, Stephan, Valentine, John, Wang, Ming-Hsi, Zonca, Martin, Rioux, John, Duerr, Richard, Silverberg, Mark, Cho, Judy, Hakonarson, Hakon, Zwick, Michael, McGovern, Dermot, and Kugathasan, Subra

Subjects
Genetic Analysis, Risk Factor, SNP, Trans-Ethnic, Adenylyl Cyclases, Black or African American, Case-Control Studies, Cell Adhesion Molecules, Neuronal, Colitis, Ulcerative, Crohn Disease, GPI-Linked Proteins, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotyping Techniques, HLA-DQ alpha-Chains, HLA-DRB1 Chains, Humans, Interleukin-12 Subunit p40, KCNQ2 Potassium Channel, Polymorphism, Single Nucleotide, Receptors, CXCR6, Receptors, Chemokine, Receptors, Interleukin, Receptors, Prostaglandin E, EP4 Subtype, Receptors, Virus, Repressor Proteins, Sorting Nexins, Tenascin, Ubiquitin Thiolesterase, White People
Abstract

BACKGROUND & AIMS: The inflammatory bowel diseases (IBD) ulcerative colitis (UC) and Crohns disease (CD) cause significant morbidity and are increasing in prevalence among all populations, including African Americans. More than 200 susceptibility loci have been identified in populations of predominantly European ancestry, but few loci have been associated with IBD in other ethnicities. METHODS: We performed 2 high-density, genome-wide scans comprising 2345 cases of African Americans with IBD (1646 with CD, 583 with UC, and 116 inflammatory bowel disease unclassified) and 5002 individuals without IBD (controls, identified from the Health Retirement Study and Kaiser Permanente database). Single-nucleotide polymorphisms (SNPs) associated at P

Published
2017

8. Characterization of Genetic Loci That Affect Susceptibility to Inflammatory Bowel Diseases in African Americans

Author

Huang, Chengrui, Haritunians, Talin, Okou, David T, Cutler, David J, Zwick, Michael E, Taylor, Kent D, Datta, Lisa W, Maranville, Joseph C, Liu, Zhenqiu, Ellis, Shannon, Chopra, Pankaj, Alexander, Jonathan S, Baldassano, Robert N, Cross, Raymond K, Dassopoulos, Themistocles, Dhere, Tanvi A, Duerr, Richard H, Hanson, John S, Hou, Jason K, Hussain, Sunny Z, Isaacs, Kim L, Kachelries, Kelly E, Kader, Howard, Kappelman, Michael D, Katz, Jeffrey, Kellermayer, Richard, Kirschner, Barbara S, Kuemmerle, John F, Kumar, Archana, Kwon, John H, Lazarev, Mark, Mannon, Peter, Moulton, Dedrick E, Osuntokun, Bankole O, Patel, Ashish, Rioux, John D, Rotter, Jerome I, Saeed, Shehzad, Scherl, Ellen J, Silverberg, Mark S, Silverman, Ann, Targan, Stephan R, Valentine, John F, Wang, Ming-Hsi, Simpson, Claire L, Bridges, S Louis, Kimberly, Robert P, Rich, Stephen S, Cho, Judy H, Di Rienzo, Anna, Kao, Linda WH, McGovern, Dermot PB, Brant, Steven R, and Kugathasan, Subra

Subjects
Genetics, Clinical Research, Crohn's Disease, Digestive Diseases, Inflammatory Bowel Disease, Autoimmune Disease, Aetiology, 2.1 Biological and endogenous factors, Oral and gastrointestinal, Good Health and Well Being, Adult, Black or African American, Aged, Colitis, Ulcerative, Crohn Disease, Female, Genetic Loci, Genetic Predisposition to Disease, Humans, Inflammatory Bowel Diseases, Male, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors, United States, White People, Young Adult, Race, Ethnicity, Genetic Variant, Intestinal Inflammation, Clinical Sciences, Neurosciences, Paediatrics and Reproductive Medicine, Gastroenterology & Hepatology
Abstract

Background & aimsInflammatory bowel disease (IBD) has familial aggregation in African Americans (AAs), but little is known about the molecular genetic susceptibility. Mapping studies using the Immunochip genotyping array expand the number of susceptibility loci for IBD in Caucasians to 163, but the contribution of the 163 loci and European admixture to IBD risk in AAs is unclear. We performed a genetic mapping study using the Immunochip to determine whether IBD susceptibility loci in Caucasians also affect risk in AAs and identify new associated loci.MethodsWe recruited AAs with IBD and without IBD (controls) from 34 IBD centers in the United States; additional controls were collected from 4 other Immunochip studies. Association and admixture loci were mapped for 1088 patients with Crohn's disease, 361 with ulcerative colitis, 62 with IBD type unknown, and 1797 controls; 130,241 autosomal single-nucleotide polymorphisms (SNPs) were analyzed.ResultsThe strongest associations were observed between ulcerative colitis and HLA rs9271366 (P = 7.5 × 10(-6)), Crohn's disease and 5p13.1 rs4286721 (P = 3.5 × 10(-6)), and IBD and KAT2A rs730086 (P = 2.3 × 10(-6)). Additional suggestive associations (P < 4.2 × 10(-5)) were observed between Crohn's disease and IBD and African-specific SNPs in STAT5A and STAT3; between IBD and SNPs in IL23R, IL12B, and C2orf43; and between ulcerative colitis and SNPs near HDAC11 and near LINC00994. The latter 3 loci have not been previously associated with IBD, but require replication. Established Caucasian associations were replicated in AAs (P < 3.1 × 10(-4)) at NOD2, IL23R, 5p15.3, and IKZF3. Significant admixture (P < 3.9 × 10(-4)) was observed for 17q12-17q21.31 (IZKF3 through STAT3), 10q11.23-10q21.2, 15q22.2-15q23, and 16p12.2-16p12.1. Network analyses showed significant enrichment (false discovery rate

Published
2015

18. IBD Serology and Disease Outcomes in African Americans With Crohn’s Disease

Author

Bertha, Madeline, Vasantharoopan, Arthi, Kumar, Archana, Bruce, Beau B, Prince, Jarod, Hofmekler, Tatyana, Okou, David, Chopra, Pankaj, Wang, Gabriel, Sauer, Cary, Landers, Carol J, Hussain, Sunny Z, Cross, Raymond K, Baldassano, Robert N, Kappelman, Michael D, Katz, Jeffrey, Alexander, Jonathan S, Kirschner, Barbara S, Moulton, Dedrick E, Osuntokun, Bankole O, Patel, Ashish, Saeed, Shehzad, Klapproth, Jan-Michael A, Dhere, Tanvi A, Dubinsky, Marla C, McGovern, Dermot, and Kugathasan, Subra

Published
2018
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23. P026 Inflammatory Bowel Disease (IBD) Related Outcomes in Patients Diagnosed With COVID-19

Author

Lue Nicole, Woolard Lisa, Jewell Lisa, Eskreis David, Prasad Meena, Naidu Harini, Iskandar Heba, Dhere Tanvi, and Spandorfer Adam

Subjects
medicine.medical_specialty, Hepatology, Coronavirus disease 2019 (COVID-19), business.industry, Internal medicine, Gastroenterology, medicine, MEDLINE, In patient, medicine.disease, business, Inflammatory bowel disease
Published
2021

26. S3355 Inflammatory Bowel Disease (IBD) Patients in Remission at the Time of COVID-19 Diagnosis Have Better IBD Related Outcomes Than Those With Moderate Disease Activity at the Time of COVID-19 Diagnosis

Author

Spandorfer, Adam, primary, Lue, Nicole, additional, Iskandar, Heba N., additional, Naidu, Harini, additional, Jewell, Lisa, additional, Eskreis, David, additional, Woolard, Lisa M., additional, Prasad, Meena, additional, and Dhere, Tanvi, additional

Published
2021
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30. Diagnostic and therapeutic considerations for obscure gastrointestinal bleeding in patients with chronic kidney disease

Author

Muftah, Mayssan, Mulki, Ramzi, Dhere, Tanvi, Keilin, Steven, and Chawla, Saurabh

Subjects
Obscure gastrointestinal bleeding, angiodysplasia, small-bowel bleeding, Review Article, arteriovenous malformations, chronic kidney disease
Abstract

Recurrent obscure gastrointestinal bleeding amongst patients with chronic kidney disease is a challenging problem gastroenterologists are facing and is associated with an extensive diagnostic workup, limited therapeutic options, and high healthcare costs. Small-bowel angiodysplasia is the most common etiology of obscure and recurrent gastrointestinal bleeding in the general population. Chronic kidney disease is associated with a higher risk of gastrointestinal bleeding and of developing angiodysplasia compared with the general population. As a result, recurrent bleeding in this subgroup of patients is more prevalent and is associated with an increased number of endoscopic and radiographic procedures with uncertain benefit. Alternative medical therapies can reduce re-bleeding; however, more studies are needed to confirm their efficacy in this subgroup of patients.

Published
2018

40. Mo1954 – Fecal Microbiota Transplantation is Safe and Effective for the Treatment of Clostridium Difficile Infection in Patients with Liver Cirrhosis

Author

Cheng, Yao-Wen, primary, Alhaffar, Dana, additional, Saha, Srishti, additional, Khanna, Sahil, additional, Bohm, Matthew, additional, Phelps, Emmalee, additional, Ghabril, Marwan S., additional, Orman, Eric, additional, Sagi, Sashidhar, additional, Xu, Huiping, additional, Khoruts, Alexander, additional, Vaughn, Byron P., additional, Kao, Dina H., additional, Wong, Karen, additional, Cammarota, Giovanni, additional, Ianiro, Gianluca, additional, Dhere, Tanvi A., additional, Kraft, Colleen, additional, Mehta, Nirja, additional, Woodworth, Michael H., additional, Allegretti, Jessica R., additional, Nativ, Lotem, additional, El-Nachef, Najwa, additional, and Fischer, Monika, additional

Published
2019
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41. Su1028 – Whole-Genome Sequencing of African Americans Identifies Novel Rare Variants Associated with Inflammatory Bowel Disease

Author

Somineni, Hari K., primary, Haritunians, Talin, additional, Simpson, Claire L., additional, Cutler, David J., additional, Okou, David, additional, Itan, Yuval, additional, Venkateswaran, Suresh, additional, Stevens, Christine, additional, Datta, Lisa W., additional, Dhere, Tanvi A., additional, Lazarev, Mark, additional, Consortium, Emory African American IBD, additional, Zwick, Michael E., additional, Cho, Judy H., additional, Daly, Mark J., additional, McGovern, Dermot, additional, Brant, Steven R., additional, and Kugathasan, Subra, additional

Published
2019
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50. Tacrolimus concentration to dose ratio in solid organ transplant patients treated with fecal microbiota transplantation for recurrent Clostridium difficile infection

Author

Woodworth, Michael H., primary, Kraft, Colleen S., additional, Meredith, Erika J., additional, Mehta, Aneesh K., additional, Wang, Tiffany, additional, Mamo, Yafet T., additional, Dhere, Tanvi, additional, Sitchenko, Kaitlin L., additional, Patzer, Rachel E., additional, and Friedman-Moraco, Rachel J., additional

Published
2018
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