Dataset Information

Weighted Genetic Risk Scores and Prediction of Weight Gain in Solid Organ Transplant Populations.

ABSTRACT:

Background

Polygenic obesity in Solid Organ Transplant (SOT) populations is considered a risk factor for the development of metabolic abnormalities and graft survival. Few studies to date have studied the genetics of weight gain in SOT recipients. We aimed to determine whether weighted genetic risk scores (w-GRS) integrating genetic polymorphisms from GWAS studies (SNP group#1 and SNP group#2) and from Candidate Gene studies (SNP group#3) influence BMI in SOT populations and if they predict ?10% weight gain (WG) one year after transplantation. To do so, two samples (nA = 995, nB = 156) were obtained from naturalistic studies and three w-GRS were constructed and tested for association with BMI over time. Prediction of 10% WG at one year after transplantation was assessed with models containing genetic and clinical factors.

Results

w-GRS were associated with BMI in sample A and B combined (BMI increased by 0.14 and 0.11 units per additional risk allele in SNP group#1 and #2, respectively, p-values<0.008). w-GRS of SNP group#3 showed an effect of 0.01 kg/m2 per additional risk allele when combining sample A and B (p-value 0.04). Models with genetic factors performed better than models without in predicting 10% WG at one year after transplantation.

Conclusions

This is the first study in SOT evaluating extensively the association of w-GRS with BMI and the influence of clinical and genetic factors on 10% of WG one year after transplantation, showing the importance of integrating genetic factors in the final model. Genetics of obesity among SOT recipients remains an important issue and can contribute to treatment personalization and prediction of WG after transplantation.

SUBMITTER: Saigi-Morgui N

PROVIDER: S-EPMC5082801 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

Weighted Genetic Risk Scores and Prediction of Weight Gain in Solid Organ Transplant Populations.

Saigi-Morgui Núria N Quteineh Lina L Bochud Pierre-Yves PY Crettol Severine S Kutalik Zoltán Z Wojtowicz Agnieszka A Bibert Stéphanie S Beckmann Sonja S Mueller Nicolas J NJ Binet Isabelle I van Delden Christian C Steiger Jürg J Mohacsi Paul P Stirnimann Guido G Soccal Paola M PM Pascual Manuel M Eap Chin B CB

PloS one 20161027 10

<h4>Background</h4>Polygenic obesity in Solid Organ Transplant (SOT) populations is considered a risk factor for the development of metabolic abnormalities and graft survival. Few studies to date have studied the genetics of weight gain in SOT recipients. We aimed to determine whether weighted genetic risk scores (w-GRS) integrating genetic polymorphisms from GWAS studies (SNP group#1 and SNP group#2) and from Candidate Gene studies (SNP group#3) influence BMI in SOT populations and if they pred ...[more]

PMID: 27788139

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Project description:BackgroundOverweight and obesity, which have a substantial impact on health in the general population, have similar prevalence in solid organ transplant recipients but carry even more serious ramifications. As this group's use of immunosuppressive medication increases the risk for comorbidities, e.g. metabolic syndrome and cardiovascular disease, the prevention of additional risk factors is vital. This systematic review will be the first to summarize the issue of weight gain, overweight and obesity concurrently within and across solid organ transplantation. The three research questions relating to solid organ transplantation are the following: (1) What are the prevalence and evolution of overweight and obesity from pre- to post-transplant?; (2) Which pre- and post-transplant risk factors are associated with post-transplant weight gain, overweight or obesity? and (3) Which post-transplant patient outcomes and comorbidities are associated with pre- and post-transplant weight gain, overweight and obesity?Methods/designMEDLINE via PubMed, The Cochrane Library, Cumulative Index to Nursing and Allied Health (CINAHL), PsycINFO and Excerpta Medica DataBase (EMBASE) will be searched for original quantitative studies in adult liver, heart, lung or kidney transplant patients. Topics of interest will be the prevalence and evolution of overweight and obesity over time, risk factors associated with changes in weight or body mass index (BMI), overweight and obesity, and the relationship of weight or BMI with post-transplant outcomes and comorbidities. Screening of titles and abstracts, full-text reading and data extraction will be divided between three researchers. Researchers will cross-check one another's screening decisions for random samples of studies to adhere as closely as possible to the recommendations of The Cochrane Collaboration. For quality assessment, a purpose-adapted 19-item instrument will be used. Effect sizes will be calculated for relationships investigated in a minimum of five studies. Random effects meta-analysis with moderator analyses will be conducted if applicable.DiscussionThis systematic review will comprehensively synthesize the existing evidence concerning weight gain, overweight and obesity in solid organ transplantation in view of magnitude, influencing factors and associations with patient outcomes and comorbidities. The results can fuel the development of interventions to prevent weight gain in the solid organ transplant population.Systematic review registrationPROSPERO CRD42014009151.

Project description:Importance:Presumed consent, or an opt-out organ transplant policy, has been adopted by many countries worldwide to increase organ donation. The implication of such a policy for transplants in the United States is uncertain, however. Objective:To simulate the potential implications of a presumed consent policy in the United States. Design, Setting, and Participants:In a decision analytical model, a simulation model was developed using cohort data from January 1, 2004, to December 31, 2014, in the Organ Procurement and Transplantation Network Standard Transplant Analysis and Research files. All US patients (n = 524 359) who were on the waiting list for at least 1 solid organ and all deceased organ donors during the study period were included in the analyses. All data and statistical analyses were performed from January 30, 2019, to July 31, 2019. Main Outcomes and Measures:Increase in the organs available for donation and life-years gained associated with a 5%, 15%, or 25% increase in deceased donors, based on the published changes from a presumed consent policy. Results:This study considered 524 359 unique candidates (aged ≥18 years; 320 908 [61.2%] male) for a solid organ transplant from January 1, 2004, to December 31, 2014. With a base case scenario of a 5% presumed consent-associated increase in donors, the removals (owing to death or illness) from the waiting list for all organs would have an associated 3.2% to 10.4% mean reduction, depending on the random or ideal allocation of new organs to patients on the waiting list. Sensitivity analyses showed that waiting list removals could be decreased up to 52%; however, this reduction was not enough to completely eliminate waiting list removals during the study period. The biggest estimated increases in annual life-years gained associated with a presumed consent policy were in kidney transplant candidates (95% CIs by deceased donor increase: 5% increase, 3440-3466 years; 15% increase, 10 321-10 399 years; 25% increase, 17 201-17 332 years) and liver transplant candidates (95% CIs by deceased donor increase: 5% increase, 898-905 years; 15% increase, 2693-2714 years; 25% increase, 4448-4523 years). Adoption of a presumed consent policy could result in a 4295-year (95% CI, 4277-4313 years) to 11 387-year (95% CI, 11 339-11 435 years) increase in life-years, accounting for the survival advantages associated with a transplant. Conclusions and Relevance:In this study, presumed consent was estimated to be associated with modest but important improvement in the number of organ transplants and increases in life-years gained for patients awaiting an organ transplant. Further consideration and even debate about the ethical and public policy implications of a presumed consent policy are warranted.

Project description:BACKGROUND:Immunosuppressed solid organ transplant recipients [SOTRs] have elevated rates of certain rare cancers caused by viruses. Evaluating risk of rare cancers among SOTRs may provide etiological clues for additional cancers linked to poor immunity and viral infections. METHODS:We performed a cohort study of 262,455 SOTRs (1987-2014) from the US SOTR registry linked to 17 population-based cancer registries. First cancers in SOTRs were categorized using an established classification scheme based on site and histology. Standardized incidence ratios (SIRs) compared risk in SOTRs to the general population. We used Poisson regression to calculate incidence rate ratios (IRRs) according to immune-related SOTR characteristics, including time since transplant (i.e., duration of immunosuppression). All statistical tests are two-sided. RESULTS:We examined 694 distinct cancer subtypes, with 33 manifesting statistically significantly elevated SIRs (Bonferroni p?<?7.2 x 10-5). All 33 are rare (incidence <6 per 100,000 person-years) and several have known viral etiology (e.g. Merkel cell carcinoma (SIR = 24.7, 95%CI = 20.8 to 29.1). Additional cancers that were increased include squamous cell carcinomas (SCCs) of the lip (SIR range = 18.3-19.8), eye/adnexa (SIR = 13.8, 95%CI = 7.9 to 22.3), salivary gland (SIR = 9.3, 95%CI = 6.1 to 13.5), and nasal cavity/sinuses (SIR = 4.5, 95%CI = 2.8 to 6.8); sebaceous adenocarcinoma (SIR = 34.3, 95%CI = 26.3 to 44.0); malignant fibrous histiocytoma (15.4); and subtypes of bladder, kidney, lung, and colon cancer (SIR range = 3.2-13.3). Incidence of several cancers increased over time since transplant (ptrend<0.05), including SCCs of the lip, salivary gland, and anogenital sites. CONCLUSIONS:SOTRs experience elevated rates of several rare cancers. Because some of these cancers exhibit aggressive behavior with poor outcomes, it is important to further characterize the role of immunity and the potential involvement of oncogenic viruses to improve prevention and treatment.

Dataset Information

Weighted Genetic Risk Scores and Prediction of Weight Gain in Solid Organ Transplant Populations.

Background

Results

Conclusions

Publications

Weighted Genetic Risk Scores and Prediction of Weight Gain in Solid Organ Transplant Populations.

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