title: Recent Advances in Human Genetics and Epigenetics of Adiposity: Pathway to Precision Medicine?
abstract: Obesity is a heritable trait that contributes to substantial global morbidity and mortality. Here, we summarize findings from the past decade of genetic and epigenetic research focused on unravelling the underpinnings of adiposity. More than 140 genetic regions now are known to influence adiposity traits. The genetics of general adiposity, as measured by body mass index, and that of abdominal obesity, as measured by waist-to-hip ratio, have distinct biological backgrounds. Gene expression associated with general adiposity is enriched in the nervous system. In contrast, genes associated with abdominal adiposity function in adipose tissue. Recent population-based epigenetic analyses have highlighted additional distinct loci. We discuss how associated genetic variants can lead to understanding causal mechanisms, and to disentangling reverse causation in epigenetic analyses. Discoveries emerging from population genomics are identifying new disease markers and potential novel drug targets to better define and combat obesity and related diseases.
authors.affiliation: Department of Medical Sciences and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Tove
authors.initials: T
authors.lastname: Fall
authors.affiliation: The Framingham Heart Study, Framingham, Massachusetts; Population Sciences Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland; Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts.
authors.forename: Michael
authors.initials: M
authors.lastname: Mendelson
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan. Electronic address: espeliot@med.umich.edu.
authors.forename: Elizabeth K
authors.initials: EK
authors.lastname: Speliotes
mesh_terms: D050154:Adiposity / Q000235:genetics*; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO / Q000235:genetics; D000818:Animals; D015992:Body Mass Index; D044127:Epigenesis, Genetic; D015870:Gene Expression; D058685:Genetic Pleiotropy; D055106:Genome-Wide Association Study; D023281:Genomics; D006801:Humans; D009765:Obesity / Q000188:drug therapy / Q000235:genetics*; D056128:Obesity, Abdominal / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D057285:Precision Medicine; D044469:Racial Groups / Q000235:genetics
chemical_list: D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO
keywords: Adiposity; Epigenetics; Genetics; Obesity