title: [Genetics of obesity].
abstract: Animal models and family studies led to the identification ofcases of rare monogenic forms of human obesity. Rare Mendelian syndromes as Prader-Willi syndrome and Bardet-Biedl syndrome represent cases of genetically determined obesity. Genome wide linkage and classical candidate gene studies were in general unsuccessful concerning the identification of genes of common obesity. On the other hand, genome-wide association studies (GWAS) were found to be effective, as also variants with only a minor effect have been detected. Seventeen polygenic variants influencing body weight regulation were clearly confirmed. It is assumed that more of these variants exist and therefore they might be identified in near future by GWAS. It is possible that the size effect of some variants can be within few grams of body weight. In order to detect variants with small effect there is a need of meta-analyses based on hundreds of thousands of individuals. Newly identified variants result in an increase of 0.06-0.33 kg/m2 of BMI per allele. In an adult of an average height of 170cm, it corresponds to 173-954 g per risk allele. It was estimated that subjects carrying 13 or more risk alleles were on average 1.46 body mass index units heavier (representing 3.7-4.7 kg) than carriers of less than three risk alleles. Further research should be focused on a gene-gene interaction. An interaction ofgene and environment should be statistically analyzed in adequate proband cohorts. If we are able to identify a large number of risk variants, the predisposition to a certain disease could be predicted. Currently a detailed family history has more predictive power.
authors.affiliation: Klinika detí a dorostu 3. lékarské fakulty UK a FN Královské Vinohrady Praha, Centrum pro výzkum diabetu, metabolismu a výzivy. ihainer@hotmail.com
authors.forename: Irena Aldhoon
authors.initials: IA
authors.lastname: Hainerová
mesh_terms: D056769:Alstrom Syndrome / Q000235:genetics; D020788:Bardet-Biedl Syndrome / Q000235:genetics; D001835:Body Weight / Q000235:genetics; D044127:Epigenesis, Genetic; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D009765:Obesity / Q000453:epidemiology / Q000235:genetics*; D011218:Prader-Willi Syndrome / Q000235:genetics