Polygenic contribution to obesity: genome-wide strategies reveal new targets.
Obesity results from the complex interaction of environmental factors that act on a genetic background that determines the susceptibility to obesity. The identification of such obesity susceptibility genes can provide important insights into the mechanism underlying this condition. While candidate gene approaches have not been tremendously successful in identifying relevant genetic contributors to obesity, except PPAR , the advent of genome-wide strategies has recently revealed novel and unexpected genetic factors with strong associations with obesity and/or diabetes, i.e. FTO, TCF7L2, INSIG2, ENPP1, or FASN (reviewed herein), although some of them are not undebated. Considering the function of the encoded proteins, it will now be of interest to investigate the cellular and molecular mechanisms, how these genetic variations affect body weight, energy metabolism and/or obesity-associated morbidity.
Körner
Antje
A
University Hospital for Children and Adolescents, Research Laboratory, University of Leipzig, Leipzig, Germany.
Kiess
Wieland
W
Stumvoll
Michael
M
Kovacs
Peter
P
D000328:Adult; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D002648:Child; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D054890:Fatty Acid Synthase, Type I / Q000235:genetics; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D015894:Genome, Human; D006801:Humans; D007198:Indians, North American / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D009765:Obesity / Q000235:genetics*; D047495:PPAR gamma / Q000235:genetics; D010727:Phosphoric Diester Hydrolases / Q000235:genetics / Q000502:physiology; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics; D011755:Pyrophosphatases / Q000235:genetics / Q000502:physiology; D011972:Receptor, Insulin / Q000502:physiology; D012307:Risk Factors; D051820:TCF Transcription Factors / Q000235:genetics; D058118:Transcription Factor 7-Like 2 Protein
C467727:INSIG2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D047495:PPAR gamma; D011506:Proteins; D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human; C518729:FASN protein, human; D054890:Fatty Acid Synthase, Type I; D011972:Receptor, Insulin; D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; D011755:Pyrophosphatases