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Clinical Research

Phenotypic and genetic analysis of an adult cohort with extreme obesity

International Journal of Obesity volume 43, pages 2057–2065 (2019)Cite this article

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Abstract

Context:

Adult extreme obesity (EO) is a growing health concern. The prevalence of known obesity associated co-morbidities namely cardio-metabolic and neuro-psychiatric disease in EO is not fully established. The contribution of pathogenic genetic variants, previously implicated in early childhood onset obesity, to adult EO is also not established.

Objective:

We undertook phenotypic and genetic analysis of adult patients with extreme obesity (EO, BMI > 50). Specifically, we assessed the prevalence of eating disorders, cardio-metabolic, and neuro-psychiatric disease and the presence of pathogenic variants in known monogenic obesity genes.

Design:

A total of 55 patients with EO from a single site bariatric surgery referral program were assessed for the presence of eating disorders, cardio-metabolic, and neuro-psychiatric disease. The 54 obese (O) patients with a BMI < 50 from the same program were identified for phenotypic comparison. The 45 EO patients underwent whole exome sequencing to identify deleterious variants in known monogenic obesity genes.

Outcomes:

(1) Presence of eating disorders, cardio-metabolic, and neuro-psychiatric disease in EO compared to O. (2) Onset of obesity in the EO group. (3) Presence of deleterious variants in genes previously implicated in monogenic obesity in the EO group.

Results:

The EO group had higher prevalence of lifetime neuro-psychiatric disease (67.3% vs. 37%, p = 0.001) and sleep apnea (74.6% vs. 51.9%, p = 0.01) but lower prevalence of type 2 diabetes (30.1% vs. 50%, p = 0.045) compared to O. There were no significant differences in binge eating, dyslipidemia, hypertension, and cardiac disease. In the EO group, we found previously unreported singleton variants in NTRK2 (pS667W, bio-informatically predicted to be deleterious) and BDNF (pE23K). No previously confirmed loss of function variants in monogenic obesity genes were found.

Conclusions:

Adults with EO have significantly increased prevalence of neuro-psychiatric disease and a possibly lower burden of type 2 diabetes compared to less obese patients. Known monogenic causes of obesity were not highly prevalent in this cohort. Further studies are warranted to confirm these preliminary findings.

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Acknowledgements

This work has been funded by Toronto General Hospital Research Institute and Diabetes Canada. PS is a recipient of a Diabetes Action Canada Post-Doctoral Fellowship. SD is a recipient of a Diabetes Canada New Investigator Award and Banting and Best Diabetes Center, Toronto Dennis Scholarship. The authors would like to thank Christina Drake, RN and Suzana Tavares, RN for their help in recruiting and assessing patients.

Author contributions

SD, SSo, AP, PS, AB, TJ, AO, DU, JA designed the study. SD, PS, SSu, and SJL. SD and PS wrote the manuscript with input from all the authors. SD is the guarantor of this work.

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Authors and Affiliations

  1. Department of Medicine and Endocrinology, University of Toronto, Toronto, ON, Canada

    Priska Stahel, Shawn K. Sud, So Jeong Lee & Satya Dash

  2. Division of General Surgery, University Health Network, Toronto, ON, Canada

    Timothy Jackson

  3. Department of Surgery, Faculty of Medicine, University of Toronto, Toronto, ON, Canada

    Timothy Jackson, David R. Urbach & Allan Okrainec

  4. Bariatric Surgery Department, Toronto Western Hospital, Toronto, ON, Canada

    Allan Okrainec & Sanjeev Sockalingam

  5. Department of Medicine, University of Toronto, Toronto, ON, Canada

    Johane P. Allard

  6. Department of Nutritional Sciences, University of Toronto, Toronto, ON, Canada

    Johane P. Allard

  7. The Dalglish Family 22q Clinic for Adults with 22q11.2 Deletion Syndrome, University Health Network, Toronto, ON, Canada

    Anne S. Bassett

  8. Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, ON, Canada

    Anne S. Bassett

  9. Department of Psychiatry, University of Toronto, Toronto, ON, Canada

    Anne S. Bassett

  10. Department of Psychiatry, University Health Network, Toronto, ON, Canada

    Anne S. Bassett

  11. Division of Cardiology, Department of Medicine, and Toronto General Research Institute, University Health Network, Toronto, ON, Canada

    Anne S. Bassett

  12. Program in Genetics and Genome Biology, The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON, Canada

    Andrew D. Paterson

  13. Division of Epidemiology and Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada

    Andrew D. Paterson

  14. Centre for Mental Health, University Health Network, Toronto, ON, Canada

    Sanjeev Sockalingam

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  1. Priska Stahel
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Correspondence to Satya Dash.

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Stahel, P., Sud, S.K., Lee, S.J. et al. Phenotypic and genetic analysis of an adult cohort with extreme obesity. Int J Obes 43, 2057–2065 (2019). https://doi.org/10.1038/s41366-018-0209-8

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