The obesity-associated gene <i>Negr1</i>
 regulates aspects of energy balance in rat hypothalamic areas

Boender, Arjen J.; Gestel, M A van; Garner, Keith M.; Luijendijk, Mieneke C. M.; Adan, Roger A.H.

doi:10.14814/phy2.12083

Cited by 40 publications

(44 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous research has identified this gene as a possible 468 susceptibility gene for obesity (Yanagiya et al 2007); however, relatively little is known about any 469 functional consequences of SNPs within this pseudogene. We also observed a strongly associated locus 470 in NEGR1, one of the first genes shown to have variants associated to BMI (Thorleifsson et al 2008;471 Willer et al 2009;Speliotes et al 2010;Boender et al 2014). This gene codes for a cell adhesion 472 molecule, although its function in relation to BMI is still unknown.…”

supporting

confidence: 62%

“…Furthermore, 77% of the SNPs in this second GWAS (21/27) were previously associated 306 with BMI in previous research studies (Scuteri et al 2007;Frayling et al 2007;Dina et al 2007;307 Zeggini et al 2007;Yanagiya et al 2007;Hinney et al 2007;Hunt et al 2008;Price et al 2008;Grant 308 et al 2008;Hotta et al 2008;Loos et al 2008;Tan et al 2008;Villalobos-Comparán et al 2008;309 Thorleifsson et al 2008;Willer et al 2009;Meyre et al 2009;Wing et al 2009;Liu et al 2009;310 Shimaoka et al 2010;Fawcett and Barroso 2010;Speliotes et al 2010;Wang et al 2011;Prakash et 311 al. 2011;Okada et al 2012;Cha et al 2012;Berndt et al 2013;Wheeler et al 2013;Graff et al 2013;312 Olza et al 2013;Boender et al 2014;Christensen et al 2015;Nakajima et al 2016;Thomsen et al 313 2016;Qureshi et al 2017;Huđek et al 2018;Gonzalez-Herrera et al 2018). With the addition of DM2 314 as a covariate, the GWAS identified several additional SNPs on chromosome 8, as well as SNPs on 315 chromosomes 17 and 19.…”

Section: Gwas Of Bmi In the Healthy Nevada Cohort 266mentioning

confidence: 99%

“…This gene codes for a cell adhesion 472 molecule, although its function in relation to BMI is still unknown. Previous research in mice 473 determined that deletions of NEGR1 cause a decrease in weight and a change in the regulation of 474 energy balance, implying that NEGR1 most likely functions to control the regulation of energy balance 475 (Lee et al 2012;Boender et al 2014). 476…”

mentioning

confidence: 99%

See 2 more Smart Citations

A Comprehensive Genome-wide and Phenome-wide Examination of BMI and Obesity in a Northern Nevadan Cohort

Schlauch

Read

Lombardi

et al. 2019

Preprint

View full text Add to dashboard Cite

21The aggregation of Election Health Records (EHR) and personalized genetics leads to powerful 22 discoveries relevant to population health. Here we perform genome-wide association studies (GWAS) 23 and accompanying phenome-wide association studies (PheWAS) to validate phenotype-genotype 24 associations of BMI, and to a greater extent, severe Class 2 obesity, using comprehensive diagnostic 25 and clinical data from the EHR database of our cohort. Three GWASs of 500,000 variants on the 26 Illumina platform of 6,645 Healthy Nevada participants identified several published and novel variants 27 that affect BMI and obesity. Each GWAS was followed with two independent PheWASs to examine 28 associations between extensive phenotypes (incidence of diagnoses, condition, or disease), significant 29 SNPs, BMI, and incidence of extreme obesity. The first GWAS excludes DM2-diagnosed individuals 30 and focuses on associations with BMI exclusively. The second GWAS examines the interplay between 31 Type 2 Diabetes (DM2) and BMI. The intersection of significant variants of these two studies is 32 surprising. The third complementary case-control GWAS, with cases defined as extremely obese (Class 33 2 or 3 obesity), identifies strong associations with extreme obesity, including established variants in the 34 FTO and NEGR1 genes, as well as loci not yet linked to obesity. The PheWASs validate published 35 associations between BMI and extreme obesity and incidence of specific diagnoses and conditions, yet 36 also highlight novel links. This study emphasizes the importance of our extensive longitudinal EHR 37 database to validate known associations and identify putative novel links with BMI and obesity. 38 39 2014; Qureshi et al. 2017; Huđek et al. 2018; Gonzalez-Herrera et al. 2018), none, to the best of our 63 knowledge, have included comprehensive GWASs on the quantitative BMI metric and on extreme 64 obesity case-control simultaneously, as well as investigated phenotypic associations with BMI, obesity, 65 and significant loci identified by the GWAS. 66 67 Our study begins with the Healthy Nevada Project (HNP), a project centered around a Northern Nevada 68 cohort formed in 2016 and 2017 by Renown Health and the Desert Research Institute in Reno, NV to 69 4investigate factors that may contribute to health outcomes in Northern Nevada. Its first phase provided 70 10,000 individuals in Northern Nevada with genotyping using the 23andMe platform at no cost. 71Renown Health is the only tertiary care health system in the area, and 75% of these 10,000 individuals 72 are cross-referenced in its extensive electronic health records (EHR) database. The Renown EHR 73 database contains 86,610 BMI measurements for these 10,000 individuals over twelve years, along 74 with comprehensive disease diagnoses, (e.g. diabetes or eating disorders) and other general conditions 75 such as pregnancy, allowing for precise individual phenotypic classifications and thereby leading to 76 more robust and meaningful phenotype-genotype associations. 77 78The focus ...

show abstract

supporting

confidence: 62%

Section: Gwas Of Bmi In the Healthy Nevada Cohort 266mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

A Comprehensive Genome-wide and Phenome-wide Examination of BMI and Obesity in a Northern Nevadan Cohort

Schlauch

Read

Lombardi

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…Furthermore, an association between NEGR1 and obesity has been reported by Wheeler et al [2013] and Boender et al [2014]. These authors found that decreased expression of NEGR1 in periventricular hypothalamic areas of rats led to an increase in body weight, presumably via increased food intake.…”

Section: Discussionmentioning

confidence: 79%

“…As Kilon is found chiefly at axons and presynaptic terminals, it can be mainly expressed at the dendritic postsynaptic spine of neurons [Alvarez and Sabatini, 2007]. NEGR1 has become of great interest based on the recent findings that its genetic alteration is implicated in human obesity and human dyslexia [Willer et al, 2009;Veerappa et al, 2013;Wheeler et al, 2013;Boender et al, 2014]. As NEGR1 is involved in neurite outgrowth [Schäfer et al, 2005], a process known to be involved in human obesity [Farooqi and O'Rahilly, 2007], these observations could form the basis for a molecular explanation for this association, which needs to be experimentally tested.…”

Section: Discussionmentioning

confidence: 99%

Clinical and Molecular Cytogenetic Characterization of a de novo Interstitial 1p31.1p31.3 Deletion in a Boy with Moderate Intellectual Disability and Severe Language Impairment

Tassano¹,

Gamucci

Celle

et al. 2015

Cytogenet Genome Res

View full text Add to dashboard Cite

Interstitial 1p deletions are rare events. Very few cases of 1p31.1p31.3 deletions characterized by variable phenotypes have been reported. No clear genotype-phenotype correlation has been determined yet. We present a child with a de novo interstitial 1p31.1p31.3 deletion, identified by array CGH, associated with intellectual disability and severe language impairment. The deleted region contains 20 OMIM genes, but we focused on GADD45A (MIM 126335; growth arrest- and DNA damage-inducible gene), LRRC7 (MIM 614453; leucine-rich repeat-containing protein 7), and NEGR1 (MIM 613173; neuronal growth regulator 1). We discuss whether these genes play a role in determining the phenotype of our patient in order to investigate the possibility of a genotype-phenotype correlation.

show abstract

Genetics and epigenetics in the obesity phenotyping scenario

Trang

Grant

2023

Rev Endocr Metab Disord

View full text Add to dashboard Cite

Obesity is a common complex trait that elevates the risk for various diseases, including type 2 diabetes and cardiovascular disease. A combination of environmental and genetic factors influences the pathogenesis of obesity. Advances in genomic technologies have driven the identification of multiple genetic loci associated with this disease, ranging from studying severe onset cases to investigating common multifactorial polygenic forms. Additionally, findings from epigenetic analyses of modifications to the genome that do not involve changes to the underlying DNA sequence have emerged as key signatures in the development of obesity. Such modifications can mediate the effects of environmental factors, including diet and lifestyle, on gene expression and clinical presentation. This review outlines what is known about the genetic and epigenetic contributors to obesity susceptibility, along with the albeit limited therapeutic options currently available. Furthermore, we delineate the potential mechanisms of actions through which epigenetic changes can mediate environmental influences and the related opportunities they present for future interventions in the management of obesity.

show abstract

The obesity-associated gene Negr1 regulates aspects of energy balance in rat hypothalamic areas

Cited by 40 publications

References 23 publications

A Comprehensive Genome-wide and Phenome-wide Examination of BMI and Obesity in a Northern Nevadan Cohort

A Comprehensive Genome-wide and Phenome-wide Examination of BMI and Obesity in a Northern Nevadan Cohort

Clinical and Molecular Cytogenetic Characterization of a de novo Interstitial 1p31.1p31.3 Deletion in a Boy with Moderate Intellectual Disability and Severe Language Impairment

Genetics and epigenetics in the obesity phenotyping scenario

Contact Info

Product

Resources

About