Bulimia Nervosa, Susceptibility To

Description

Bulimia nervosa (BN) is a psychiatric disorder characterized by episodes of binge-eating (eating an unusually large amount of food in a discrete period of time and feeling out of control), compensatory behavior (e.g., self-induced vomiting or laxative abuse), and over-concern with weight and shape.

Eating disorders such as bulimia nervosa are complex disorders that can be influenced by many genes.

Inheritance

There is evidence that bulimia (as well as the related eating disorder anorexia nervosa (AN; see 606788) and eating disorders not otherwise specified) is strongly familial (Lilenfeld et al., 1998; Strober et al., 2000; Bulik et al., 2000). Twin studies estimate the heritability of syndromic bulimia to be 54 to 83% (Kendler et al., 1991; Bulik et al., 1998; Wade et al., 1999; Kortegaard et al., 2001).

Mapping

Bulik et al. (2003) conducted a linkage analysis in multiplex families with eating disorders that were identified through a proband with bulimia nervosa. Linkage analysis of the entire sample of 308 families yielded a double peak, with the highest nonparametric multiplex maximum lod score (MLS) of 2.92 on chromosome 10. Given the high heritability of self-induced vomiting and the reliability with which it could be measured, Bulik et al. (2003) performed linkage analysis in a subset of 133 families in which at least 2 affected relatives reported a symptom pattern that included self-induced vomiting. The highest MLS (3.39) observed was on chromosome 10, between markers D10S1430 and D10S1423. These results provided evidence for the presence of a susceptibility locus (BULN1) for bulimia nervosa on 10p. Another region on 14q met the criterion for genomewide suggestive linkage, with MLSs of 1.97 (full sample) and 1.75 (subset) at 62 cM from the end of 14p.

Bacanu et al. (2005) measured over 100 attributes thought to be related to liability to eating disorders in affected individuals of multiplex families from the AN cohort that had previously been studied by Grice et al. (2002) and Devlin et al. (2002) and the BN cohort that had previously been studied by Bulik et al. (2003). Six traits were selected for linkage analysis on the basis of expert evaluation and statistical analysis, including obsessionality, age at menarche, anxiety for quantitative trait locus (QTL) linkage analysis, lifetime minimum body mass index (BMI), concern over mistakes, and food-related obsessions. Using QTL linkage analysis, the BN cohort produced 4 suggestive signals: for age at menarche at 10p13 and for anxiety for QTL linkage analysis at 1q31.1, 4q35.2, and 8q13.1. Using covariate-based linkage analysis, the BN cohort showed the most significant and suggestive linkages: for minimum BMI, 1 significant linkage at 4q21.1 and 3 suggestive linkages at 3p23, 10p13, and 5p15.3; for concern over mistakes, 2 significant linkages at 16p13.3 and 14q21.1 and 3 suggestive linkages at 4p15.33, 8q11.23, and 10p11.21; and for food-related obsessions, 1 significant linkage at 14q21.1 and 5 suggestive linkages at 4p16.1, 10p13.1, 8q11.23, 16p13.3, and 18p11.31. For the AN cohort, results were less compelling. Using QTL linkage analysis, they found 2 suggestive linkages, for obsessionality at 6q21 and for anxiety for QTL linkage analysis at 9p21.3. Covariate-based linkage analysis of the AN cohort revealed 5 suggestive signals: for minimum BMI at 4q13.1, for concern over mistakes, at 11p11.2 and 17q25.1, and for food-related obsessions at 17q25.1 and 15q26.2. There was minimum overlap between the 2 cohorts for substantial linkage signals.

Molecular Genetics

Monteleone and Maj (2008) reviewed the genetics of eating disorders, including bulimia nervosa, and stated that there was no convincing evidence for association of candidate genes with eating disorders; they noted that the heterogeneity of eating disorder phenotypes was most likely responsible for the contradictory and inconclusive results.

Associations Pending Confirmation

For discussion of an association between susceptibility to bulimia (formerly symbolized BULN2) and polymorphism in the BDNF gene, see 113505.0002 and 113505.0003.