Chipping Away the ‘Missing Heritability’ GIANT Steps Forward in the Molecular Elucidation of Obesity – but Still Lots to Go英文文献.pdfVIP

Review Article Obes Facts 2010;3:294–303 Published online: October 15, 2010 DOI: 10.1159/000321537 Chipping Away the ‘Missing Heritability’: GIANT Steps Forward in the Molecular Elucidation of Obesity – but Still Lots to Go Johannes Hebebrand Anna-Lena Volckmar Nadja Knoll Anke Hinney Department of Child and Adolescent Psychiatry and Psychotherapy, University of Duisburg-Essen, Essen, Germany Keywords Monogenic Obesity and Major Gene Effects Synthetic association · Major gene · Polygene The cloning and initial detection of mutations in the mouse Summary and human leptin gene [2, 3] marked the beginning of the Although heritability of human body weight is assumed large-scale elucidation of DNA variation underlying inter- to be high, only a small fraction of the variance can as individualdifferencesinbodyweight.Currently,severaltypes yet be attributed to molecular genetic factors. Single ofmonogenicformsofobesityhavebeenidentified [4].Allof monogenic forms of obesity have been identified. Func- the respective mutations are rare, some have only been re- tionally relevant coding mutations in the melanocor- portedin single casesworldwide; therespective genes are all tin-4 receptor gene occur in 1–6% of extremely obese expressedinthehypothalamus.Theelucidationofsuchmuta- children and adolescents and thus represent