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Diabetes. 2019 Sep 10. pii: db181254. doi: 10.2337/db18-1254. [Epub ahead of print]

Evaluation of the Genetic Association Between Adult Obesity and Neuropsychiatric Disease.

Author information

1
Department of Medicine & Endocrinology, Banting & Best Diabetes Center, University of Toronto, Toronto, ON, Canada.
2
Centre for Obesity Research, Rayne Institute, Department of Medicine, University College London, London, United Kingdom.
3
University College London Hospital (UCLH) Bariatric Centre for Weight Management and Metabolic Surgery, University College London Hospital, London, UK and.
4
National Institute of Health Research, UCLH Biomedical Research Centre, London, UK.
5
Division of General Surgery, University Health Network, Toronto, ON, Canada.
6
Department of Surgery, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
7
Toronto Western Hospital, Bariatric Surgery Department, Toronto, ON, Canada.
8
Department of Medicine, University of Toronto, Toronto, ON, Canada.
9
Department of Nutritional Sciences, University of Toronto, Toronto, ON, Canada.
10
Division of Epidemiology and Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, CanadaCentre for Mental Health, University Health Network, Toronto, ON, Canada.
11
Division of Nephrology, Department of Medicine, Toronto General Research Institute, University Health Network, Toronto, ON, Canada.
12
Karolinska Institutet, Department of Medicine, Huddinge, 141 86 Stockholm, Sweden.
13
Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.
14
The Dalglish Family 22q Clinic for Adults with 22q11.2 Deletion Syndrome, University Health Network, Toronto, ON, Canada.
15
Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, ON, Canada.
16
Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
17
Department of Psychiatry, University Health Network, Toronto, ON, Canada.
18
Division of Cardiology, Department of Medicine, and Toronto General Research Institute, University Health Network, Toronto, ON, Canada.
19
Program in Genetics and Genome Biology, The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON, Canada.
20
Department of Medicine & Endocrinology, Banting & Best Diabetes Center, University of Toronto, Toronto, ON, Canada satya.dash@uhn.ca.

Abstract

Extreme obesity (EO, BMI>50) is frequently associated with neuropsychiatric disease (NPD). As both EO and NPD are heritable central nervous system disorders, we assessed the prevalence of protein truncating (PTV) and copy number variants (CNV) in genes/regions previously implicated in NPD, in adults with EO (n=149) referred for weight loss/bariatric surgery. We also assessed the prevalence of CNVs in patients referred to University College London Hospital (UCLH) with EO (n=218) and obesity (O, BMI 35-50, n=374) and a Swedish cohort of participants from the community with predominantly O (n=161). The prevalence of variants was compared to controls in ExAC/gnomAd database.In the discovery cohort (high NPD prevalence: 77%), the cumulative PTV/CNV allele frequency (AF) was 7.7 % vs 2.6% in controls (Odds Ratio (OR) 3.1, (95% CI 2-4.1, p<0.0001). In the UCLH EO cohort (intermediate NPD prevalence: 47%), CNV AF (1.8% vs 0.9% in controls, OR 1.95, 95% CI 0.96-3.93, p=0.06) was lower than the discovery cohort. CNV AF was not increased in the UCLH O cohort (0.8%). No CNVs were identified in the Swedish cohort with no NPD.These findings suggest PTV/CNVs, in genes/regions previously associated with NPD, may contribute to NPD in patients with EO.

PMID:
31506345
DOI:
10.2337/db18-1254

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