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Evaluation of the Genetic Association Between Adult Obesity and Neuropsychiatric Disease
- Stahel, P (author)
- Nahmias, A (author)
- Sud, SK (author)
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- Lee, SJ (author)
- Pucci, A (author)
- Yousseif, A (author)
- Youseff, A (author)
- Jackson, T (author)
- Urbach, DR (author)
- Okrainec, A (author)
- Allard, JP (author)
- Sockalingam, S (author)
- Yao, T (author)
- Barua, M (author)
- Magi, R (author)
- Bassett, AS (author)
- Paterson, AD (author)
- Batterham, RL (author)
- Dash, S (author)
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- (creator_code:org_t)
- 2019-09-10
- 2019
- English.
- In: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 68:12, s. 2235-2246
- Journal article (peer-reviewed)
Abstract
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- Extreme obesity (EO) (BMI >50 kg/m2) 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 variants (PTVs) and copy number variants (CNVs) 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 kg/m2; n = 374) and a Swedish cohort of participants from the community with predominantly O (n = 161). The prevalence of variants was compared with control subjects in the Exome Aggregation Consortium/Genome Aggregation Database. In the discovery cohort (high NPD prevalence: 77%), the cumulative PTV/CNV allele frequency (AF) was 7.7% vs. 2.6% in control subjects (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 control subjects; 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 that PTV/CNVs, in genes/regions previously associated with NPD, may contribute to NPD in patients with EO.
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- Stahel, P
- Nahmias, A
- Sud, SK
- Lee, SJ
- Pucci, A
- Yousseif, A
- show more...
- Youseff, A
- Jackson, T
- Urbach, DR
- Okrainec, A
- Allard, JP
- Sockalingam, S
- Yao, T
- Barua, M
- Jiao, H
- Magi, R
- Bassett, AS
- Paterson, AD
- Dahlman, I
- Batterham, RL
- Dash, S
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- Diabetes
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- Karolinska Institutet
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