Genetic factors in anorexia nervosa

Abstract

Anorexia nervosa is a severe and complex disorder with incompletely known vulnerability factors. It is generally recognized that anorexia nervosa is a familial disorder, but the majority of twin studies have shown that the concordance rate for monozygotic twins is higher (on average 44%) than for dizygotic twins (on average 12.5%). This difference in concordance rates shows that genetic factors, more than common familial environment, may explain why the 'anorexia nervosa' phenotype runs in families. In order to estimate the heritability in the broad sense of anorexia nervosa according to published familial and twin studies, we first assessed the intrapair correlation between monozygotic and dizygotic twins, and secondly calculated the deviation threshold of relatives of affected probands from the relative mean. In this review, we obtained an estimation of the heritability at 0.72 according to all published controlled familial studies (six references quoted in MEDLINE(R)), and 0.71 for all published twin studies (59 references quoted in MEDLINE(R)). This estimation is close to the ones previously proposed, between 0. 5 and 0.8. Familial and twin studies may also help to define the boundaries of the phenotype, shedding light on the complex relationship between anorexia nervosa on the one hand, and bulimia nervosa, mood disorders, and alcoholism on the other. Demonstrating the importance of genetic factors in anorexia nervosa, and more specifically for anorexia of the restrictive type, requires not only prospective and adoption studies (which are still lacking), but also genetic polymorphisms analyses, which began very recently.

Perceptions of illness in individuals with anorexia nervosa: A comparison with lay men and women

“…Although this view is in keeping with the clinical and research literature on AN, the presence of strong internal attributions may also have a negative impact on mental health. It is noteworthy that hereditary factors were not commonly endorsed as a cause of AN, despite evidence of a substantial genetic component (Bulik, Sullivan, Wade, & Kendler, 2000;Kipman, Gorwood, Mouren-Simeoni, & Ades, 1999). Lay responses to an open-ended question about understanding of the term anorexia nervosa were similar to those found in an earlier study by Huon et al (1988), suggesting that overall, public conceptualization of AN has not changed.…”

Association between anorexia nervosa and the hsKCa3 gene: a family-based and case control study

“…The genotyping of hSKCa3 polymorphic alleles was based on the analysis of PCR fragments generated with 5Ј-end Cy5-labeled forward primer: 5Ј-AAGTGCCCCTGT CCATCCTCT-3Ј, and reverse primer: 5Ј-GCCAAGCAAGTGGTCATTGAG-3Ј. 5 Polymerase chain reaction (PCR) conditions were: 95°C-5 min initial denaturation; 35 cycles of 95°C-1 min, 65°C-1 min, and 72°C-1 min; 72°C-5 min final extension. The PCR products were analyzed on the ALF Express DNA analysis system (Pharmacia, Uppsala, Sweden) against an external size marker (50-500 bp scale) (supplied by the manufacturer), and internal size marker, added to each sample.…”

“…[1][2][3][4][5] The hSKCa3 potassium channel gene, which contains polymorphic CAG repeats in the coding region and is involved in the regulation of neuronal activity, may be a candidate gene for AN because alleles with longer repeats have been found to be associated with mental disorders. 6 Forty Israeli AN family trios were genotyped for the hSKCa3 CAG repeat polymorphism using the haplotype relative risk (HRR) method.…”

“…4 AN is a complex disorder probably caused by multiple genes, each contributing to the genetic predisposition. 5 The heterogeneity of AN phenotypes and the high rate of comorbidity of major depression disorder, generalized anxiety, and obsessive-compulsive disorder [7][8][9][10] suggest that AN may share common genetic factors with other mental disorders.…”

Association between serotonin transporter gene polymorphism and eating disorders: A meta‐analytic study

“…Although the pathogenesis of EDs is still unclear, evidence from family and twin studies suggests a substantial genetic susceptibility to them. It is estimated that genetic variances account for 50-70% of the risk factors for AN [1][2][3] and 28-83% for BN. 2,[4][5][6] Serotonin (5-HT) has been shown to play a critical role in regulating appetite.…”