TY - JOUR
T1 - Evidence for at least two major loci influencing human fatness
AU - Borecki, Ingrid B.
AU - Blangero, John
AU - Rice, Treva
AU - Pérusse, Louis
AU - Bouchard, Claude
AU - Rao, D. C.
N1 - Funding Information:
This work was supported, in part, by National Institutes of Health grants GM28719 and HD18281 and by Medical Research Council of Canada grants MT13960 and PG11811.
PY - 1998/9
Y1 - 1998/9
N2 - The genetics of human fatness has been the subject of many recent studies, motivated by the increased morbidity and mortality associated with obesity, as well as the increasing prevalence of overweight and obesity. The body-mass index (BMI) and fat mass (FM), measured by underwater weighing, were assessed for 1,630 individuals from ~300 families from phase 1 of the Quebec Family Study. The two phenotypes are highly correlated (~.8) in adults, and previous segregation analysis revealed evidence for a recessive major gene for each trait. In our study, we utilized bivariate segregation analysis to determine the source(s) of phenotypic correlation - namely, a pleiotropic major gene, shared familial factors/polygenes, or shared nontransmitted environmental factors. Analysis was performed by use of the Pedigree Analysis Package, with extensions to the bivariate case. Tests of hypotheses provided evidence for two pleiotropic recessive loci, together accounting for 64% and 47% of the variance in BMI and FM, respectively. Under the model, all sources of phenotypic correlation were significant: 73% of the covariance was attributed to the pleiotropic major loci, 8% to residual familial effects, and 19% to nontransmitted environmental factors. The high degree of genetic identity between the two traits is not surprising, since the BMI often is used as a surrogate for FM; however, simultaneous analysis of both phenotypes enabled the detection of a second major locus, which apparently does not affect extreme overweight (as does the primary major locus) but which affects variation in the 'normal' range.
AB - The genetics of human fatness has been the subject of many recent studies, motivated by the increased morbidity and mortality associated with obesity, as well as the increasing prevalence of overweight and obesity. The body-mass index (BMI) and fat mass (FM), measured by underwater weighing, were assessed for 1,630 individuals from ~300 families from phase 1 of the Quebec Family Study. The two phenotypes are highly correlated (~.8) in adults, and previous segregation analysis revealed evidence for a recessive major gene for each trait. In our study, we utilized bivariate segregation analysis to determine the source(s) of phenotypic correlation - namely, a pleiotropic major gene, shared familial factors/polygenes, or shared nontransmitted environmental factors. Analysis was performed by use of the Pedigree Analysis Package, with extensions to the bivariate case. Tests of hypotheses provided evidence for two pleiotropic recessive loci, together accounting for 64% and 47% of the variance in BMI and FM, respectively. Under the model, all sources of phenotypic correlation were significant: 73% of the covariance was attributed to the pleiotropic major loci, 8% to residual familial effects, and 19% to nontransmitted environmental factors. The high degree of genetic identity between the two traits is not surprising, since the BMI often is used as a surrogate for FM; however, simultaneous analysis of both phenotypes enabled the detection of a second major locus, which apparently does not affect extreme overweight (as does the primary major locus) but which affects variation in the 'normal' range.
UR - http://www.scopus.com/inward/record.url?scp=0032231716&partnerID=8YFLogxK
U2 - 10.1086/302006
DO - 10.1086/302006
M3 - Article
C2 - 9718336
AN - SCOPUS:0032231716
SN - 0002-9297
VL - 63
SP - 831
EP - 838
JO - American journal of human genetics
JF - American journal of human genetics
IS - 3
ER -