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Evaluation of the Genetic Association Between Adult Obesity and Neuropsychiatric Disease

Stahel, P; Nahmias, A; Sud, SK; Lee, SJ; Pucci, A; Yousseif, A; Yosseff, A; ... Dash, S; + view all (2019) Evaluation of the Genetic Association Between Adult Obesity and Neuropsychiatric Disease. Diabetes , 68 (12) pp. 2235-2246. 10.2337/db18-1254. (In press). Green open access

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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.

Type: Article
Title: Evaluation of the Genetic Association Between Adult Obesity and Neuropsychiatric Disease
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.2337/db18-1254
Publisher version: https://doi.org/10.2337/db18-1254
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10083663
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