Polygene Formen der Adipositas und Störungs-übergreifende Analysen

J. Giuranna; J. Antel; L. Libuda; T. Reinehr; T. Peters; J. Hebebrand; A. Hinney

doi:10.1055/s-0038-1676674

Adipositas - Ursachen, Folgeerkrankungen, Therapie, Inhaltsverzeichnis

Adipositas - Ursachen, Folgeerkrankungen, Therapie 2018; 12(04): 176-182
DOI: 10.1055/s-0038-1676674

Übersichtsarbeit

Georg Thieme Verlag KG Stuttgart · New York

Polygene Formen der Adipositas und Störungs-übergreifende Analysen

Polygenic forms of obesity and cross-trait analyses

Autoren

J. Giuranna

¹Klinik für Psychiatrie, Psychosomatik und Psychotherapie des Kindes- und Jugendalters, Universitätsklinikum Essen (AöR), Universität Duisburg-Essen, Essen
J. Antel

¹Klinik für Psychiatrie, Psychosomatik und Psychotherapie des Kindes- und Jugendalters, Universitätsklinikum Essen (AöR), Universität Duisburg-Essen, Essen
L. Libuda

¹Klinik für Psychiatrie, Psychosomatik und Psychotherapie des Kindes- und Jugendalters, Universitätsklinikum Essen (AöR), Universität Duisburg-Essen, Essen
T. Reinehr

²Vestische Kinder- und Jugendklinik Datteln, Abteilung für Endokrinologie, Diabetologie und Pädiatrische Ernährungsmedizin, Universität Witten/Herdecke
T. Peters

¹Klinik für Psychiatrie, Psychosomatik und Psychotherapie des Kindes- und Jugendalters, Universitätsklinikum Essen (AöR), Universität Duisburg-Essen, Essen
J. Hebebrand

¹Klinik für Psychiatrie, Psychosomatik und Psychotherapie des Kindes- und Jugendalters, Universitätsklinikum Essen (AöR), Universität Duisburg-Essen, Essen
A. Hinney

¹Klinik für Psychiatrie, Psychosomatik und Psychotherapie des Kindes- und Jugendalters, Universitätsklinikum Essen (AöR), Universität Duisburg-Essen, Essen

Abstract

Zusammenfassung

Neben monogenen Formen und Hauptgen-Effekten sind für die genetische Prädisposition zur Adipositas polygene Mechanismen relevant. Meta-Analysen von genom-weiten Assoziationsstudien (GWAMA) haben mehr als 700 polygene Loci oder Polygene identifiziert, die genom-weit mit dem Body Mass index (BMI) assoziiert sind. Diese prädisponierenden Genvarianten (Allele) finden sich bei adipösen Probanden häufiger als bei normalgewichtigen oder schlanken Individuen. Mittels statistischer Analysen wurden diese Allele als Adipositas-Risikoallele klassifiziert. Jede einzelne polygene Variante leistet nur einen kleinen Beitrag zur Entwicklung einer Adipositas und erhöht das Gewicht pro Risikoallel nur um ca. hundert Gramm bis 1,5 Kilogramm. Der Erfolg der GWAMA hat in letzter Zeit Phänotyp übergreifende, sogenannte Cross- Disorder- und Cross-Phänotyp-Analysen, ermöglicht. Dabei können Risiko-Gene identifiziert werden, die mittels Analysen der einzelnen Erkrankungen / Phänotypen nicht entdeckt werden konnten. Funktionelle Studien (in vitro und in vivo) der GWAMA-abgeleiteten Polygene können zu einem besseren Verständnis der Mechanismen der Körpergewichtsregulation führen.

Summary

In addition to monogenic and major gene effects, polygenic mechanisms are relevant for the genetic predisposition to obesity. Metaanalyses of genome-wide association studies (GWAMA) have identified more than 700 genome-wide polygenic loci or polygenes associated with Body Mass index (BMI). These predisposing gene variants (alleles) can be found in obese subjects more often than in normal weight or lean individuals. By means of statistical analyses, these alleles were classified as obesity risk alleles. Each individual polygenic variant provides only a small contribution to the development of obesity, so that a specific risk allele increases the weight by about one hundred grams to 1.5 kilograms. The success of GWAMA(s) has recently enabled cross-disorder and cross phenotype analyses to be performed across different phenotypes/traits. Genes that could not be detected by analyses of the individual traits/phenotypes could then be identified. Functional studies (in vitro and in vivo) of the GWAMA-derived polygenes can lead to a better understanding of the mechanisms of body weight regulation.

Schlüsselwörter

Genom-weite Assoziationsstudien - Melanocortin-4 Rezeptorgen - „Fat mass and obesity associated” Gen (FTO)

Keywords

Genome-wide association studies - melanocortin-4 receptor gene - fat mass and obesity associated gene (FTO)

Volltext

Referenzen

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