A genome-wide association study on common SNPs and rare CNVs in anorexia nervosa

Wang, K; Zhang, H; Bloss, Cinnamon S.; Duvvuri, Vikas; Kaye, Walter H.; Schork, Nicholas J.; Berrettini, Wade H.; Hákonarson, Hákon

doi:10.1038/mp.2010.107

Cited by 196 publications

(197 citation statements)

References 81 publications

Supporting

Mentioning

189

Contrasting

Unclassified

Order By: Relevance

“…In contrast, no associations were found for AN risk, which is consistent with the findings by Brandys et al. (2010), who failed to find a significant effect of a KCTD15 polymorphism previously associated with obesity in AN patients; as well as with several GWAS, which have not identified any KCTD15 SNP related to AN risk (Boraska et al., 2014; Hinney et al., 2017; Wang et al., 2011). In this regard, several loci in or near KCTD15 have repeatedly been associated with obesity in a number of GWAS and replication studies (Mei et al., 2012; Paternoster et al., 2011; Thorleifsson et al., 2009; Willer et al., 2009).…”

Section: Discussionmentioning

confidence: 99%

Influence of TFAP2B and KCTD15 genetic variability on personality dimensions in anorexia and bulimia nervosa

et al. 2017

View full text Add to dashboard Cite

Introduction TFAP2B and KCTD15 are obesity‐related genes that interact to regulate feeding behavior. We hypothesize that variability in these loci, isolated or in combination, could also be related to the risk of eating disorders (ED) and/or associated psychological traits.MethodsWe screened 425 participants (169 ED patients, 75 obese subjects, and 181 controls) for 10 clinically relevant and tag single‐nucleotide polymorphisms (SNPs) in KCTD15 and TFAP2B by the Sequenom MassARRAY platform and direct sequencing. Psychometric evaluation was performed with EDI‐2 and SCL‐90R inventories.ResultsThe KCTD15 rs287103 T variant allele was associated with increased risk of bulimia nervosa (BN) (OR = 4.34 [1.47–29.52]; p = .003) and with scores of psychopathological scales of these patients. Haplotype *6 in KCTD15 was more frequent in controls (OR = 0.40 [0.20–0.80], p = .009 for anorexia nervosa), while haplotype *4 in TFAP2B affected all three scales of the SCL‐90R inventory in BN patients (p ≤ .01). Epistasis analyses revealed relevant interactions with body mass index of BN patients (p < .001). Genetic profiles in obese patients did not significantly differ from those found in ED patients.ConclusionsThis is the first study that evaluates the combined role of TFAP2B and KCTD15 genes in ED. Our preliminary findings suggest that the interaction of genetic variability in these loci could influence the risk for ED and/or anthropometric and psychological parameters.

show abstract

Section: Discussionmentioning

confidence: 99%

Influence of TFAP2B and KCTD15 genetic variability on personality dimensions in anorexia and bulimia nervosa

et al. 2017

View full text Add to dashboard Cite

show abstract

“…EDs are thought to occur as a result of a complex interaction between genetic predisposition and environmental risk factors. While genetic factors are estimated to contribute 50%-80% of the risk of developing an ED (2), to date, several studies using both genome-wide analysis (3,4) and candidate gene (5) approaches have failed to identify specific genes that predispose to the development of an ED. One alternative approach to large-scale linkage and association studies is to characterize rare single-gene mutations in large families severely affected by mental illness.…”

Section: Introductionmentioning

confidence: 99%

Eating disorder predisposition is associated with ESRRA and HDAC4 mutations

Cui¹,

Moore²,

Ashimi³

et al. 2013

J. Clin. Invest.

View full text Add to dashboard Cite

Anorexia nervosa and bulimia nervosa are common and severe eating disorders (EDs) of unknown etiology. Although genetic factors have been implicated in the psychopathology of EDs, a clear biological pathway has not been delineated. DNA from two large families affected by EDs was collected, and mutations segregating with illness were identified by whole-genome sequencing following linkage mapping or by whole-exome sequencing. In the first family, analysis of twenty members across three generations identified a rare missense mutation in the estrogen-related receptor α (ESRRA) gene that segregated with illness. In the second family, analysis of eight members across four generations identified a missense mutation in the histone deacetylase 4 (HDAC4) gene that segregated with illness. ESRRA and HDAC4 were determined to interact both in vitro in HeLa cells and in vivo in mouse cortex. Transcriptional analysis revealed that HDAC4 potently represses the expression of known ESRRA-induced target genes. Biochemical analysis of candidate mutations revealed that the identified ESRRA mutation decreased its transcriptional activity, while the HDAC4 mutation increased transcriptional repression of ESRRA. Our findings suggest that mutations that result in decreased ESRRA activity increase the risk of developing EDs.

show abstract

“…Nevertheless, only few studies have evaluated possible association between the NTNG1 gene polymorphisms and diseased conditions. Among those are genome wide association study shown no association between common SNPs of the NTNG1 gene and anorexia nervosa in Europeans [50], study of Zhu et al [51] demonstrated positive association of the NTNG1 gene rs4132604 SNP and the haplotype of rs4132604, rs2218404, and rs1373336 SNPs of this gene with SCZ. In addition, analyzes of 21 SNPs of the NTNG1 gene in 124 Japanese schizophrenic pedigrees revealed association of SCZ with specific haplotypes encompassing alternatively spliced exons, SNPs, and haplotypes clustered in the 5'-region of the NTNG1 gene [45].…”

Section: Resultsmentioning

confidence: 99%

Genetic Variations Associated with Brain Disorders: Focus on Synaptic Plasticity and Apoptosis Regulatory Genes in Schizophrenia, Posttraumatic Stress Disorder and Ischemic Stroke

Boyajyan¹

2014

IJGG

View full text Add to dashboard Cite

Abstract:Epidemiologic, clinical and experimental data indicates that a majority of brain disorders including schizophrenia (SCZ), posttraumatic stress disorder (PTSD), and ischemic stroke (IS) are multifactorial disorders with strong and complex genetic component. Identification of all genetic variations associated with these disorders may sufficiently contribute to understanding of their basic pathomechanisms and encourage development of new innovative approaches to their early diagnosis and treatment. The aim of this review article is to provide overview of our recent studies on evaluation of potential association of SCZ, PTSD and IS with functional single nucleotide polymorphisms (SNPs) of synaptic plasticity and apoptosis regulatory genes in Armenian population. Here, our attention was focused on genes encoding netrin G1 (NTNG1), brain-derived neurotrophic factor (BDNF), complexin-2 (CPLX2), nerve growth factor (NGF) and its receptor (NGFR), annexin family proteins -annexin A5 and annexin A11 (ANXAV, ANXA11), and B-cell lymphoma 2 (Bcl-2) family proteins -Bcl-2 proper and Bcl-2-associated X protein (BCL2, BAX). Genomic DNA samples of diseased and healthy individuals were genotyped for a number of SNPs of the mentioned genes using polymerase chain reaction with sequence-specific primers (PCR-SSP). The significance of differences in genotype and allele frequencies and minor allele carriage between patients and healthy control subjects was determined using Pearson's Chi-square test. P-values less than 0.05 were considered statistically significant. Significant associations were found between: (1) SCZ and BDNF rs6265, CPLX2 rs1366116, rs3892909, NGF rs6330, rs4839435, NGFR rs734194, rs11466155, rs2072446, ANXAV rs11575945, BAX rs1057369 SNPs; (2) PTSD and CPLX2 rs1366116, BCL2 rs956572 SNPs; (3) IS and NTNG1 rs628117, CPLX2 rs1366116, ANXAV rs11575945 SNPs. The obtained results indicated the involvement of genetically determined alterations in synaptic plasticity and apoptosis in pathomechanisms of SCZ, PTSD and IS. The minor T allele of the CPLX2 gene rs1366116 polymorphism represents risk factor for all studied diseased conditions indicating important functional significance of this genetic variation in maintenance of synaptic plasticity. Another important conclusion of these studies is that minor alleles of some polymorphic variants of genes, encoding synaptic plasticity and apoptosis regulatory proteins, may play a protective role relative to SCZ decreasing the risk for development of this disorder. In summary, our studies emphasize the important contribution of changes in synaptic plasticity and apoptosis regulation to pathomechanisms of SCZ, PTSD, and IS as well as significant input of genetic factors to these changes.

show abstract

A genome-wide association study on common SNPs and rare CNVs in anorexia nervosa

Cited by 196 publications

References 81 publications

Influence of TFAP2B and KCTD15 genetic variability on personality dimensions in anorexia and bulimia nervosa

Influence of TFAP2B and KCTD15 genetic variability on personality dimensions in anorexia and bulimia nervosa

Eating disorder predisposition is associated with ESRRA and HDAC4 mutations

Genetic Variations Associated with Brain Disorders: Focus on Synaptic Plasticity and Apoptosis Regulatory Genes in Schizophrenia, Posttraumatic Stress Disorder and Ischemic Stroke

Contact Info

Product

Resources

About