scholarly journals A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance

2012 ◽  
Vol 44 (6) ◽  
pp. 659-669 ◽  
Author(s):  
Alisa K Manning ◽  
◽  
Marie-France Hivert ◽  
Robert A Scott ◽  
Jonna L Grimsby ◽  
...  
2015 ◽  
Vol 44 (2) ◽  
pp. 700-712 ◽  
Author(s):  
N. M. Warrington ◽  
L. D. Howe ◽  
L. Paternoster ◽  
M. Kaakinen ◽  
S. Herrala ◽  
...  

Author(s):  
Duan Liu ◽  
Thanh Thanh Le Nguyen ◽  
Huanyao Gao ◽  
Huaizhi Huang ◽  
Daniel C. Kim ◽  
...  

AbstractBipolar disorder (BD) and obesity are highly comorbid. We previously performed a genome-wide association study (GWAS) for BD risk accounting for the effect of body mass index (BMI), which identified a genome-wide significant single-nucleotide polymorphism (SNP) in the gene encoding the transcription factor 7 like 2 (TCF7L2). However, the molecular function of TCF7L2 in the central nervous system (CNS) and its possible role in the BD and BMI interaction remained unclear. In the present study, we demonstrated by studying human induced pluripotent stem cell (hiPSC)-derived astrocytes, cells that highly express TCF7L2 in the CNS, that the BD-BMI GWAS risk SNP is associated with glucocorticoid-dependent repression of the expression of a previously uncharacterized TCF7L2 transcript variant. That transcript is a long non-coding RNA (lncRNA-TCF7L2) that is highly expressed in the CNS but not in peripheral tissues such as the liver and pancreas that are involved in metabolism. In astrocytes, knockdown of the lncRNA-TCF7L2 resulted in decreased expression of the parent gene, TCF7L2, as well as alterations in the expression of a series of genes involved in insulin signaling and diabetes. We also studied the function of TCF7L2 in hiPSC-derived astrocytes by integrating RNA sequencing data after TCF7L2 knockdown with TCF7L2 chromatin-immunoprecipitation sequencing (ChIP-seq) data. Those studies showed that TCF7L2 directly regulated a series of BD risk genes. In summary, these results support the existence of a CNS-based mechanism underlying BD-BMI genetic risk, a mechanism based on a glucocorticoid-dependent expression quantitative trait locus that regulates the expression of a novel TCF7L2 non-coding transcript.


2019 ◽  
Vol 185 (Supplement_1) ◽  
pp. 649-655
Author(s):  
Dara M Kusic ◽  
Wendy N Roberts ◽  
Joseph P Jarvis ◽  
Pan Zhang ◽  
Laura B Scheinfeldt ◽  
...  

Abstract Introduction: the effects of obesity on health are a concern for the military as they affect the fitness to serve of active service members, increase costs to the Military Health System, and reduce quality of life for veterans and beneficiaries. Although obesity can be influenced by behavioral and environmental factors, it has also been shown to be associated with genetic risk factors that are not fully understood. Materials and Methods: we performed a genome-wide association study of 5,251 participants in the Coriell Personalized Medicine Collaborative, which includes 2,111 Air Force participants. We applied a generalized linear model, using principal component analysis to account for population structure, and analyzed single-variant associations with body mass index (BMI) as a continuous variable, using a Bonferroni-corrected P-value threshold to account for multiplicity. Results: we identified one genome-wide significant locus, rs11670527, upstream of the ZNF264 gene on chromosome 19, associated with BMI. Conclusions: the finding of an association between rs11670527 and BMI adds to the growing body of literature characterizing the complex genetics of obesity. These efforts may eventually inform personalized interventions aimed at achieving and maintaining healthy weight.


The Lancet ◽  
2014 ◽  
Vol 383 (9933) ◽  
pp. 1990-1998 ◽  
Author(s):  
Katherine J Dick ◽  
Christopher P Nelson ◽  
Loukia Tsaprouni ◽  
Johanna K Sandling ◽  
Dylan Aïssi ◽  
...  

BMC Genetics ◽  
2003 ◽  
Vol 4 (Suppl 1) ◽  
pp. S97 ◽  
Author(s):  
Roxana Moslehi ◽  
Alisa M Goldstein ◽  
Michael Beerman ◽  
Lynn Goldin ◽  
Andrew W Bergen

2020 ◽  
Vol 34 (5) ◽  
pp. 524-531 ◽  
Author(s):  
Sophie E ter Hark ◽  
Stéphane Jamain ◽  
Dick Schijven ◽  
Bochao D Lin ◽  
Mark K Bakker ◽  
...  

Background: Antipsychotic-induced weight gain is a common and debilitating side effect of antipsychotics. Although genome-wide association studies of antipsychotic-induced weight gain have been performed, few genome-wide loci have been discovered. Moreover, these genome-wide association studies have included a wide variety of antipsychotic compounds. Aims: We aim to gain more insight in the genomic loci affecting antipsychotic-induced weight gain. Given the variable pharmacological properties of antipsychotics, we hypothesized that targeting a single antipsychotic compound would provide new clues about genomic loci affecting antipsychotic-induced weight gain. Methods: All subjects included for this genome-wide association study ( n=339) were first-episode schizophrenia spectrum disorder patients treated with amisulpride and were minimally medicated (defined as antipsychotic use <2 weeks in the previous year and/or <6 weeks lifetime). Weight gain was defined as the increase in body mass index from before until approximately 1 month after amisulpride treatment. Results: Our genome-wide association analyses for antipsychotic-induced weight gain yielded one genome-wide significant hit (rs78310016; β=1.05; p=3.66 × 10−08; n=206) in a locus not previously associated with antipsychotic-induced weight gain or body mass index. Minor allele carriers had an odds ratio of 3.98 ( p=1.0 × 10−03) for clinically meaningful antipsychotic-induced weight gain (⩾7% of baseline weight). In silico analysis elucidated a chromatin interaction with 3-Hydroxy-3-Methylglutaryl-CoA Synthase 1. In an attempt to replicate single-nucleotide polymorphisms previously associated with antipsychotic-induced weight gain, we found none were associated with amisulpride-induced weight gain. Conclusion: Our findings suggest the involvement of rs78310016 and possibly 3-Hydroxy-3-Methylglutaryl-CoA Synthase 1 in antipsychotic-induced weight gain. In line with the unique binding profile of this atypical antipsychotic, our findings furthermore hint that biological mechanisms underlying amisulpride-induced weight gain differ from antipsychotic-induced weight gain by other atypical antipsychotics.


Twin Research ◽  
2004 ◽  
Vol 7 (2) ◽  
pp. 192-196 ◽  
Author(s):  
Bastiaan T. Heijmans ◽  
A. Leo Beem ◽  
Gonneke Willemsen ◽  
Daniëlle Posthuma ◽  
P. Eline Slagboom ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document