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ABSTRACT Background Even though the evidence supporting the presence of a heritable component in the aetiology of anorexia nervosa (AN) is strong, the underlying genetic mechanisms remain poorly understood. The recent publication of a genome-wide association study (GWAS) of AN (Boraska, Mol Psychiatry, 2014) was an important step in genetic research in AN. Objective To briefly sum up strengths and weaknesses of candidate-gene and genome-wide approaches, to discuss the genome-wide association studies of AN and to make predictions about the genetic architecture of AN by comparing it to that of schizophrenia (since the diseases share some similarities and genetic research in schizophrenia is more advanced). Method Descriptive literature review. Results Despite remarkable efforts, the gene-association studies in AN did not advance our knowledge as much as had been hoped, although some results still await replication. Discussion Continuous effort of participants, clinicians and researchers remains necessary to ensure that genetic research in AN follows a similarly successful path as in schizophrenia. Identification of genetic susceptibility loci provides a basis for follow-up studies. © 2015 Wiley Periodicals, Inc. (Int J Eat Disord 2015; 48:814-825) [ABSTRACT FROM AUTHOR]

Objectives. The Val66Met polymorphism (rs6265) of the BDNF gene is a non-synonymous polymorphism, previously associated with anorexia nervosa (AN). Methods. We genotyped rs6265 in 235 patients with AN and 643 controls. Furthermore, we performed a systematic review of all case-control and family-based studies testing this SNP in AN, and combined the results in a meta-analysis. Results. The results of the case-control study were non-significant. For the meta-analysis, nine studies were identified ( ncases = 2,767; ncontrols = 3,322, ntrios = 53) and included. Primarily, the analyses indicated an association with OR of 1.11 ( P = 0.024) in the allelic contrast, and OR of 1.14 ( P = 0.025) for the dominant effect of the Met allele. However, additional analyses revealed that the first published study (from those included in the meta-analysis) overly influenced the pooled effect size (possibly due to a phenomenon known as a winner's curse). When this case-control study was replaced by a trio study ( ntrios = 293) performed on a largely overlapping sample, the effect size became smaller and non-significant, both for the allelic contrast (OR = 1.07, P = 0.156) and the dominant effect (OR = 1.07, P = 0.319). The quality of included studies was good and there was no significant heterogeneity across the effect sizes. Conclusions. Our analyses indicate that the BDNF Val66Met variant is not associated with AN at detectable levels. [ABSTRACT FROM AUTHOR]

Objectives. Brain derived neurotrophic factor (BDNF) is involved in neuroplasticity, and in the homeostatic regulation of food intake and energy expenditure. It also has a role in stress responsivity and reward processing. On the basis of its involvement in these various processes, BDNF can be hypothesized to be an important factor in the development and maintenance of anorexia nervosa (AN). This study meta-analytically summarizes investigations of serum BDNF concentrations in people currently ill with AN, in comparison to healthy controls. Methods. Seven studies measuring BDNF in serum of individuals with AN ( n == 155) and healthy controls ( n == 174) were identified and included in the meta-analysis of the mean differences between case and control groups. Results. This study confirms that AN is associated with decreased serum BDNF concentrations, in comparison to healthy controls. The combined effect size (standardized mean difference, SMD) was large (SMD == −0.96; 95% CI -1.33 to −0.59; P < 0.001). Significant heterogeneity of effect sizes was identified ( I2 == 58.3%; P < 0.001), which emerged as being primarily attributable to the first published study on the investigated association. Conclusions. The present meta-analytical summary of studies measuring circulating BDNF concentrations in women with AN and healthy controls confirms that it is significantly reduced in this patient group. Difficulties associated with the measurement of BDNF have been identified and potential confounding factors have been discussed. Current data do not allow inferences to be made about causal links between levels of circulating BDNF and AN. However, possible explanations for the relationship between BDNF and AN have been presented. [ABSTRACT FROM AUTHOR]

Abstract: Genome linkage scans and candidate gene studies have implicated the pro-opiomelanocortin (POMC) locus in traits related to food intake, metabolic function, and body mass index. Here we investigate single nucleotide polymorphisms at the POMC locus in order to evaluate the influence of its genetic variance on body fat distribution and diet in a sample of middle-aged men from The Netherlands. 366 Dutch males from the Hamlet cohort were asked detailed questions about food choice, nutrient intake and exercise. Furthermore, their weight and body fat composition were measured. Each cohort member was genotyped for a set of single nucleotide polymorphisms (SNPs) at the POMC locus. Regression analysis, adjusted for several covariates, was used to test for the association between genetic variants and the phenotypes measured. POMC variation was associated with waist:hip ratio, visceral fat and abdominal fat (rs6713532, P=0.020, 0.019, and 0.021, respectively), and nutrient choice (rs1042571, P=0.034), but in light of limited power and multiple testing these results should be taken with caution. POMC is a strong candidate for involvement in appetite regulation as supported by animal, physiological, and genetic studies and variation at the POMC locus may affect an individual''s energy intake which in turn leads to variation in body composition and body fat. [Copyright &y& Elsevier]