title: The genetics of obesity in transition.
abstract: Recent advances in human genetics have revealed a number of genes influencing the susceptibility to obesity and related conditions, but it is likely that their contribution to disease is contingent on numerous environmental factors. As the obesity epidemic has occurred over a relatively short period of recent history, use of gene-by-year of birth analysis may be a useful approach for quantifying, in aggregate, the interaction between genetic susceptibility to obesity and the numerous known and unknown environmental factors that have changed during nutrition and health transitions globally during this recent increase in obesity rates. Evidence from one family-based longitudinal study set in the United States is showcased, which points to significant increases in the effect of common genetic variants on childhood and adulthood BMI over an 80 year period spanning from 1929 to the present. First, common genetic variants previously known to be associated with age at menarche through genome-wide association analysis were examined in aggregate using a genetic risk score approach. The menarche genetic risk score, composed of 42 single-nucleotide polymorphisms (SNPs) was significantly associated with peri-pubertal BMI in both boys and girls, but the magnitude of the association was strongly dependent on year of birth, with greater effect as birth year increased. Second, a similar approach was taken using instead a BMI genetic risk score composed of 32 common variants previously found to be associated with BMI. This score was strongly associated with adulthood BMI, waist circumference, and skinfold thickness, as expected, but the magnitude of the association increased with later year of birth. Such gene-environment interactions call for greater focus on the mechanisms by which environmental factors impact the functional output of the human genome, including how epigenetic mechanisms may be altered during social, technological, nutritional, and ecological transitions.
authors: University of Minnesota, School of Public Health, Division of Epidemiology and Community Health, Minneapolis, MN 55455, USA. ewd@umn.edu
authors: Ellen W
authors: EW
authors: Demerath
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D004777:Environment; D058872:Epidemics / Q000706:statistics & numerical data*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000208:ethnology*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009765:Obesity / Q000208:ethnology* / Q000235:genetics*; D014481:United States / Q000453:epidemiology; D055815:Young Adult
references: Nat Genet. 2012 Sep;44(9):991-1005
references: 22885924
references: PLoS Genet. 2007 Jul;3(7):e115
references: 17658951
references: Am J Clin Nutr. 2012 May;95(5):1136-43
references: 22418089
references: Endocrinology. 2008 May;149(5):2062-71
references: 18218688
references: Nat Genet. 2009 Jan;41(1):25-34
references: 19079261
references: Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10604-9
references: 16009939
references: Public Health. 2007 Jul;121(7):492-6
references: 17399752
references: JAMA. 2012 Feb 1;307(5):491-7
references: 22253363
references: Nat Neurosci. 2004 Aug;7(8):847-54
references: 15220929
references: Lancet. 2000 Aug 26;356(9231):757-61
references: 11085708
references: J Clin Endocrinol Metab. 2010 Jun;95(6):3048-56
references: 20410232
references: Aging Cell. 2012 Oct;11(5):727-31
references: 22888763
references: Genomics. 2012 Mar;99(3):132-7
references: 22234326
references: Nat Genet. 2010 Nov;42(11):937-48
references: 20935630
references: Epidemiology. 2012 Mar;23(2):332-40
references: 22237295
references: J Pediatr. 2012 May;160(5):762-8
references: 22177991
references: Am J Phys Anthropol. 2013 Jan;150(1):10-20
references: 23283660
references: Am J Hum Biol. 2004 Jul-Aug;16(4):453-7
references: 15214063
references: Nat Genet. 2010 Dec;42(12):1077-85
references: 21102462
references: Eur J Pharmacol. 2000 Dec 27;410(2-3):131-145
references: 11134665
references: Environ Health Perspect. 2006 Apr;114(4):567-72
references: 16581547
references: PLoS Med. 2011 Nov;8(11):e1001116
references: 22069379
references: Nature. 2009 Oct 8;461(7265):747-53
references: 19812666
references: PLoS One. 2011;6(11):e27135
references: 22087252
references: Obesity (Silver Spring). 2011 Sep;19(9):1866-72
references: 21593801
references: PLoS Genet. 2006 Mar;2(3):e41
references: 16565746