Suggestive Evidence for Causal Effect of Leptin Levels on Risk for Anorexia Nervosa: Results of a Mendelian Randomization Study

Frontiers in Genetics

Roaa Naaresh¹  Nicola Albers¹  Triinu Peters¹  Johannes Hebebrand¹  Anke Hinney¹  Jochen Antel¹  Manuel Föcker²  Lars Libuda³  Björn-Hergen Laabs⁴  Judith Bühlmeier⁵ 

[1] Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Essen, University of Duisburg-Essen, Essen, Germany;Department of Child and Adolescent Psychiatry, University of Münster, Münster, Germany;Evangelisches Krankenhaus Düsseldorf, Children’s Hospital, Düsseldorf, Germany;Institut für Medizinische Biometrie und Statistik, Universität zu Lübeck, Universitätsklinikum Schleswig-Holstein, Lübeck, Germany;Institute of Nutrition, Consumption and Health, Faculty of Natural Sciences, Paderborn University, Paderborn, Germany;

关键词: leptin levels;    anorexia nervosa;    mendelian randomization (MR);    body mass index;    hypoleptinemia;   

DOI  :  10.3389/fgene.2021.733606

来源: DOAJ

【 摘 要 】

Genetic correlations suggest a coexisting genetic predisposition to both low leptin levels and risk for anorexia nervosa (AN). To investigate the causality and direction of these associations, we performed bidirectional two-sample Mendelian randomization (MR) analyses using data of the most recent genome-wide association study (GWAS) for AN and both a GWAS and an exome-wide-association-study (EWAS) for leptin levels. Most MR methods with genetic instruments from GWAS showed a causal effect of lower leptin levels on higher risk of AN (e.g. IVW b = −0.923, p = 1.5 × 10−4). Because most patients with AN are female, we additionally performed analyses using leptin GWAS data of females only. Again, there was a significant effect of leptin levels on the risk of AN (e.g. IVW b = −0.826, p = 1.1 × 10−04). MR with genetic instruments from EWAS showed no overall effect of leptin levels on the risk for AN. For the opposite direction, MR revealed no causal effect of AN on leptin levels. If our results are confirmed in extended GWAS data sets, a low endogenous leptin synthesis represents a risk factor for developing AN.

【 授权许可】

Unknown