Genetic contributions to the etiology of anorexia nervosa: New perspectives in molecular diagnosis and treatment (original) (raw)
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The Genetics of Anorexia Nervosa: Current Findings and Future Perspectives
International journal of child and adolescent health, 2009
Anorexia nervosa is a perplexing illness with the highest mortality rate of any psychiatric disease. In this paper, we review the genetic research on anorexia nervosa (AN). Family studies have demonstrated that anorexia nervosa is familial, and twin studies have indicated that additive genetic factors contribute to the familial aggregation. Molecular genetic research, including genomewide linkage and case control association studies, have not been successful in identifying DNA variants that are unequivocally involved in the etiology of AN. We provide a critical appraisal of these studies and discuss methodological issues that may be implicated in conflicting results. Furthermore, we discuss issues relevant to genetic research such as the importance of phenotypic refinement, the use of endophenotypes, and the implications for nosology and genetic analysis. Finally, the future of genetic research for AN is discussed in terms of genomewide association studies (GWAS) and the need for es...
Anorexia nervosa viewed as an extreme weight condition: genetic implications
Human genetics, 1995
In anorexia nervosa, psychopathological features and reduced body weight are inseparable, suggesting a prominent role of behavioral factors in achievement and maintenance of extreme underweight. Due to the considerably higher prevalence of this eating disorder in females, anorexia nervosa contributes to the left end of the distribution of the body mass index, especially in the female sex. By reviewing the relevant literature we examined whether genetic research in anorexia nervosa can profit from considering this disorder as an extreme weight condition. For this purpose we compared genetic studies pertaining to both anorexia nervosa and the heritability of the body mass index. Whereas previous genetic studies in anorexia nervosa have mostly concentrated on the assessment of the familial psychopathology, further studies are warranted that additionally attempt to analyze the complex phenotype body weight in relatives of affected probands. Further insight into pathogenetic mechanisms underlying anorexia nervosa might be gained by contrasting the epidemiological, psychopathological and prognostic factors with those in severe obesity. Thus, epidemiological studies suggest that females are more likely to develop both extreme underweight and extreme obesity. A possible explanation for this phenomenon is that the, on average, higher percentage of total body weight composed of fat mass might predispose females towards the development of both extreme weight conditions. 10
Psychiatric Genetics, 1998
Anorexia nervosa is a severe disorder which seems likely to have a multifactorial aetiology. However, several studies have stressed that genetic factors play a significant role. Epidemiological studies have shown that the lifetime risk for firstdegree relatives of a patient with an eating disorder is 6% compared to 1% among relatives of controls, and a twin study performed on 34 pairs of twins has shown a higher concordance rate in monozygotic twins (55%) compared to dizygotic twins (7%). The vulnerability component of anorexia nervosa that can be attributed to genetic influences has been estimated from twin studies to be around 70%. Despite this, few genetic studies have been performed testing the role of candidate genes which code for proteins potentially implicated in the aetiopathogenesis of the disorder. In this review, genes encoding components of the dopamine, serotonin, opiate, and noradrenaline systems are assessed for their role in anorexia nervosa. Attention is paid to psychological dimensions, clinical symptoms, co-morbidity frequency, pharmacological data, and biological measures that characterize anorexia nervosa. Psychiatr Genet 8:1-12
The genetics of anorexia nervosa collaborative study: Methods and sample description
International Journal of Eating Disorders, 2008
Objective: Supported by National Institute of Mental Health (NIMH), this 12-site international collaboration seeks to identify genetic variants that affect risk for anorexia nervosa (AN). Method: Four hundred families will be ascertained with two or more individuals affected with AN. The assessment battery produces a rich set of phenotypes comprising eating disorder diagnoses and psychological and personality features known to be associated with vulnerability to eating disorders. Results: We report attributes of the first 200 families, comprising 200 probands and 232 affected relatives. Conclusion: These results provide context for the genotyping of the first 200 families by the Center for Inherited Disease Research. We will analyze our first 200 families for linkage, complete recruitment of roughly 400 families, and then perform final linkage analyses on the complete cohort. DNA, genotypes, and phenotypes will form a national eating disorder repository maintained by NIMH and available to qualified investigators. V V
A review and primer of molecular genetic studies of anorexia nervosa
The International journal of eating disorders, 2005
Recent research on anorexia nervosa (AN) has focused on examining the genetic underpinnings of its etiology. The current article reviews molecular genetic studies that have focused on this aspect of AN development. Medline and PsychInfo literature searches, in addition to close inspection of study reference sections, were used to identify studies that examined the genetic diathesis for AN. Findings from association studies indicate some role for the serotonin system in the development of AN. Genomic regions on chromosomes 1 and 10 are also likely to harbor susceptibility genes for AN as well as a range of eating pathologies. Findings corroborate those of neurobiologic studies suggesting that alterations in serotonergic functioning may contribute to the pathogenesis of AN. Nonetheless, future molecular genetic research would benefit from larger and more sustained investigations of candidate genes in homogeneous phenotypes.
The Anorexia Nervosa Genetics Initiative: Overview and Methods
2017
Background:Genetic factors contribute to anorexia nervosa (AN); and the first genome-wide significant locus has been identified. We describe methods and procedures for the Anorexia Nervosa Genetics Initiative (ANGI), an international collaboration designed to rapidly recruit 13000 individuals with AN as well as ancestrally matched controls. We present sample characteristics and the utility of an online eating disorder diagnostic questionnaire suitable for large-scale genetic and population research.Methods:ANGI recruited from the United States (US), Australia/New Zealand (ANZ), Sweden (SE), and Denmark (DK). Recruitment was via national registers (SE, DK); treatment centers (US, ANZ, SE, DK); and social and traditional media (US, ANZ, SE). All cases had a lifetime AN diagnosis based on DSM-IV or ICD-10 criteria (excluding amenorrhea). Recruited controls had no lifetime history of disordered eating behaviors. To assess the positive and negative predictive validity of the online eatin...
Evidence for a Susceptibility Gene for Anorexia Nervosa on Chromosome 1
The American Journal of Human Genetics, 2002
Eating disorders, such as anorexia nervosa (AN), have a significant genetic component. In the current study, a genomewide linkage analysis of 192 families with at least one affected relative pair with AN and related eating disorders, including bulimia nervosa, was performed, resulting in only modest evidence for linkage, with the highest nonparametric linkage (NPL) score, 1.80, at marker D4S2367 on chromosome 4. Since the reduction of sample heterogeneity would increase power to detect linkage, we performed linkage analysis in a subset ( ) of families n p 37 in which at least two affected relatives had diagnoses of restricting AN, a clinically defined subtype of AN characterized by severe limitation of food intake without the presence of binge-eating or purging behavior. When we limited the linkage analysis to this clinically more homogeneous subgroup, the highest multipoint NPL score observed was 3.03, at marker D1S3721 on chromosome 1p. The genotyping of additional markers in this region led to a peak multipoint NPL score of 3.45, thereby providing suggestive evidence for the presence of an AN-susceptibility locus on chromosome 1p.
The Anorexia Nervosa Genetics Initiative (ANGI): Overview and methods
Contemporary clinical trials, 2018
Genetic factors contribute to anorexia nervosa (AN); and the first genome-wide significant locus has been identified. We describe methods and procedures for the Anorexia Nervosa Genetics Initiative (ANGI), an international collaboration designed to rapidly recruit 13,000 individuals with AN and ancestrally matched controls. We present sample characteristics and the utility of an online eating disorder diagnostic questionnaire suitable for large-scale genetic and population research. ANGI recruited from the United States (US), Australia/New Zealand (ANZ), Sweden (SE), and Denmark (DK). Recruitment was via national registers (SE, DK); treatment centers (US, ANZ, SE, DK); and social and traditional media (US, ANZ, SE). All cases had a lifetime AN diagnosis based on DSM-IV or ICD-10 criteria (excluding amenorrhea). Recruited controls had no lifetime history of disordered eating behaviors. To assess the positive and negative predictive validity of the online eating disorder questionnaire...
Association of Candidate Genes with Phenotypic Traits Relevant to Anorexia Nervosa
European Eating Disorders Review, 2011
This analysis is a follow-up to an earlier investigation of 182 genes selected as likely candidate genetic variations conferring susceptibility to anorexia nervosa (AN). As those initial case-control results revealed no statistically significant differences in single nucleotide polymorphisms, herein we investigate alternative phenotypes associated with AN. In 1762 females using regression