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5. Molecular genetics of bipolar disorder

Author

Kandaswamy, R.

Subjects
610
Abstract

Bipolar affective disorder has a strong genetic heritability. In the UCL laboratory, a locus on chromosome 1p36 was found to be linked to bipolar and related unipolar affective disorders with a log of the odds score above 3.00. This region was subjected to fine mapping using tests of allelic association in a case-control sample as part of this thesis in order to identify the genes involved in bipolar disorder. In addition, a GWAS was also employed to fine map other bipolar affective disorder susceptibility genes. The tests of allelic association found evidence for the involvement of the PRKCZ gene. Markers D1S243 and rs3128396 at the PRKCZ gene were significantly associated with bipolar disorder with empirical P = 0.037 and P = 0.040, respectively. Other loci encoding brain expressed proteins found to be associated in the UCL GWAS sample were the genes - GRM3 and GRM7. Therefore, these genes were sequenced using PCR-based genomic sequencing. A 3'-UTR base pair change (rs56173829) in the GRM7 gene was found to be significantly associated with the disorder, although the minor allele was more frequent in controls. A base pair mutation (rs148754219) was found in the GRM3 exon 1 two bases before the translation start codon (forming part of Kozak sequence) of a GRM3 receptor isoform. The mutation was associated with bipolar disorder (P = 0.0046, odds ratio 4.2 (95% CI 1.42-12.37)). Transcription factor binding assays and cloning experiments comparing the gene expression activity of wild-type and mutant alleles showed that the mutant allele strongly affected the reporter gene activity in SH-SY5Y and HEK293 cells. If the GRM3 Kozak sequence mutation is confirmed as an important mutation in the aetiology of bipolar disorder, then it could be used as a marker for personalised treatment for a genetic subtype of affective disorders.

Published
2013

7. Kidney, Pancreas and Liver Allocation and Distribution in the United States

Author

Smith, JM, Biggins, SW, Haselby, DG, Kim, WR, Wedd, J, Lamb, K, Thompson, B, Segev, DL, Gustafson, S, Kandaswamy, R, Stock, PG, Matas, AJ, Samana, CJ, Sleeman, EF, Stewart, D, Harper, A, Edwards, E, Snyder, JJ, Kasiske, BL, and Israni, AK

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Transplantation, Liver Disease, Kidney Disease, Organ Transplantation, Digestive Diseases, Evaluation of treatments and therapeutic interventions, 6.4 Surgery, Renal and urogenital, Oral and gastrointestinal, Humans, Kidney Transplantation, Liver Transplantation, Pancreas Transplantation, Tissue and Organ Procurement, United States, Waiting Lists, Kidney allograft, liver allograft, organ allocation, pancreas allograft, transplant waiting list, transplantation, Medical and Health Sciences, Surgery, Clinical sciences, Immunology
Abstract

Kidney transplant and liver transplant are the treatments of choice for patients with end-stage renal disease and end-stage liver disease, respectively. Pancreas transplant is most commonly performed along with kidney transplant in diabetic end-stage renal disease patients. Despite a steady increase in the numbers of kidney and liver transplants performed each year in the United States, a significant shortage of kidneys and livers available for transplant remains. Organ allocation is the process the Organ Procurement and Transplantation Network (OPTN) uses to determine which candidates are offered which deceased donor organs. OPTN is charged with ensuring the effectiveness, efficiency and equity of organ sharing in the national system of organ allocation. The policy has changed incrementally over time in efforts to optimize allocation to meet these often competing goals. This review describes the history, current status and future direction of policies regarding the allocation of abdominal organs for transplant, namely the kidney, liver and pancreas, in the United States.

Published
2012

8. Protocolized screening and detection of occult alcohol use before and after liver transplant: Lessons learned from a quality improvement initiative

Author

Lim, N, primary, Leventhal, TM, additional, Thomson, MJ, additional, Hassan, M, additional, Thompson, J, additional, Adams, A, additional, Chinnakotla, S, additional, Humphreville, V, additional, Kandaswamy, R, additional, Kirchner, V, additional, Pruett, TL, additional, Schuller, L, additional, McCarty, M, additional, and Lake, J, additional

Published
2023
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12. Pancreas

Author

Kandaswamy, R., Skeans, M.A., Gustafson, S.K., Carrico, R.J., Prentice, M.A., Israni, A.K., Snyder, J.J., and Kasiske, B.L.

Published
2016
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14. Erratum

Author

Kandaswamy, R., primary, Stock, P.G., additional, Miller, J., additional, White, J., additional, Booker, S.E., additional, Israni, A.K., additional, and Snyder, J.J., additional

Published
2022
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20. First world consensus conference on pancreas transplantation: Part I-Methods and results of literature search

Author

Boggi, U., Vistoli, F., Marchetti, P., Kandaswamy, R., Berney, T., Andres, A., Arbogast, H. P., Badet, L., Baronti, W., Bartlett, S. T., Benedetti, E., Branchereau, J., Burke, G. W. 3., Buron, F., Caldara, R., Cardillo, M., Casanova, D., Cipriani, F., Cooper, M., Cupisti, A., de Koning, E. J. P., Davide, J., Drachenberg, C., Ettorre, G. M., Fernandez Cruz, L., Fridell, J. A., Friend, P. J., Furian, L., Gaber, O. A., Gruessner, A. C., Gruessner, R. W. G., Gunton, J. E., Han, D. -J., Iacopi, S., Kauffmann, E. F., Kaufman, D., Kenmochi, T., Khambalia, H. A., Lai, Q., Langer, R. M., Maffi, P., Marselli, L., Menichetti, F., Miccoli, M., Mittal, S., Morelon, E., Napoli, N., Neri, F., Oberholzer, J., Odorico, J. S., Ollinger, R., Oniscu, G., Orlando, G., Ortenzi, M., Perosa, M., Perrone, V. G., Redfield, R. R., Ricci, C., Rigotti, P., Robertson, R. P., Ross, L. F., Rossi, M., Saudek, F., Scalea, J. R., Schenker, P., Secchi, A., Socci, C., Sousa Silva, D., Squifflet, J. P., Stock, P. G., Stratta, R. J., Terrenzio, C., Uva, P., Watson, C. C. E., White, S. A., Boggi U., Vistoli F., Marchetti P., Kandaswamy R., Berney T., Andres A., Arbogast H.P., Badet L., Baronti W., Bartlett S.T., Benedetti E., Branchereau J., Burke G.W., Buron F., Caldara R., Cardillo M., Casanova D., Cipriani F., Cooper M., Cupisti A., de Koning E.J.P., Davide J., Drachenberg C., Ettorre G.M., Fernandez Cruz L., Fridell J.A., Friend P.J., Furian L., Gaber O.A., Gruessner A.C., Gruessner R.W.G., Gunton J.E., Han D.-J., Iacopi S., Kauffmann E.F., Kaufman D., Kenmochi T., Khambalia H.A., Lai Q., Langer R.M., Maffi P., Marselli L., Menichetti F., Miccoli M., Mittal S., Morelon E., Napoli N., Neri F., Oberholzer J., Odorico J.S., Ollinger R., Oniscu G., Orlando G., Ortenzi M., Perosa M., Perrone V.G., Redfield R.R., Ricci C., Rigotti P., Robertson R.P., Ross L.F., Rossi M., Saudek F., Scalea J.R., Schenker P., Secchi A., Socci C., Sousa Silva D., Squifflet J.P., Stock P.G., Stratta R.J., Terrenzio C., Uva P., Watson C.C.E., and White S.A.

Subjects
clinical research / practice, diabetes, pancreas / simultaneous pancreas-kidney transplantation, survey, Consensus, Humans, Pancreas Transplantation, medicine.medical_treatment, media_common.quotation_subject, Delphi method, Consensu, Pancreas transplantation, Session (web analytics), Jury, Voting, medicine, Immunology and Allergy, Pharmacology (medical), Grading (education), media_common, Transplantation, Medical education, business.industry, pancreas / simultaneous pancreas‐kidney transplantation, Systematic review, diabete, Special Articles, Original Article, First World, business, Human
Abstract

Comprehensive evidence‐based guidelines for the practice of pancreas transplantation are yet to be established. The First World Consensus Conference on Pancreas Transplantation was convened for this purpose. A steering committee selected the participants and defined the questions to be addressed. A group of literature reviewers identified 597 studies to be included in summaries for guidelines production. Expert groups formulated the first draft of recommendations. Two rounds of discussion and voting occurred online, using the Delphi method (agreement rate ≥85%). After each round, critical responses of experts were reviewed, and recommendations were amended accordingly. Recommendations were finalized after live discussions. Each session was preceded by expert presentations and a summary of results of systematic literature review. Up to three voting rounds were allowed for each recommendation. To avoid potential conflicts of interest, deliberations on issues regarding the impact of pancreas transplantation on the management of diabetes were conducted by an independent jury. Recommendations on technical issues were determined by experts and validated using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. Quality of evidence was assessed using the Scottish Intercollegiate Guidelines Network (SIGN) methodology. Each recommendation received a GRADE rating (Grading of Recommendations, Assessment, Development and Evaluations)., This article presents the results of literature search and the methods used to provide evidence‐based guidelines for the practice of pancreas transplantation at the First World Consensus Conference on Pancreas Transplantation.

Published
2021

33. DNA METHYLATION PROFILING MIGHT SHED LIGHT ON THE BIOLOGY OF CANNABIS ASSOCIATED PSYCHOSIS

Author

Di Forti, M, Dempster, E, Quattrone, D, Tripoli, G, Kandaswamy, R, Morgan, C, van Os, J, Rutten, B, Murray, R, Mill, J, Wong, C, Radhakrishnan, R, Di Forti, M, Dempster, E, Quattrone, D, Tripoli, G, Kandaswamy, R, Morgan, C, van Os, J, Rutten, B, Murray, R, Mill, J, Wong, C, and Radhakrishnan, R

Subjects
DNA methylation, cannabi, psychosis
Published
2019

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