Evidence for at least two major loci influencing human fatness

Ingrid B. Borecki, John Blangero, Treva Rice, Louis Pérusse, Claude Bouchard, D. C. Rao

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)831-838
Number of pages8
JournalAmerican Journal of Human Genetics
Volume63
Issue number3
DOIs
StatePublished - Sep 1998
Externally publishedYes

Fingerprint

Body Mass Index
Fats
Pedigree
Obesity
Genetic Pleiotropy
Phenotype
Recessive Genes
Quebec
Medical Genetics
Reference Values
Morbidity
Mortality

ASJC Scopus subject areas

  • Genetics

Cite this

Borecki, I. B., Blangero, J., Rice, T., Pérusse, L., Bouchard, C., & Rao, D. C. (1998). Evidence for at least two major loci influencing human fatness. American Journal of Human Genetics, 63(3), 831-838. https://doi.org/10.1086/302006

Evidence for at least two major loci influencing human fatness. / Borecki, Ingrid B.; Blangero, John; Rice, Treva; Pérusse, Louis; Bouchard, Claude; Rao, D. C.

In: American Journal of Human Genetics, Vol. 63, No. 3, 09.1998, p. 831-838.

Research output: Contribution to journalArticle

Borecki, IB, Blangero, J, Rice, T, Pérusse, L, Bouchard, C & Rao, DC 1998, 'Evidence for at least two major loci influencing human fatness', American Journal of Human Genetics, vol. 63, no. 3, pp. 831-838. https://doi.org/10.1086/302006
Borecki IB, Blangero J, Rice T, Pérusse L, Bouchard C, Rao DC. Evidence for at least two major loci influencing human fatness. American Journal of Human Genetics. 1998 Sep;63(3):831-838. https://doi.org/10.1086/302006
Borecki, Ingrid B. ; Blangero, John ; Rice, Treva ; Pérusse, Louis ; Bouchard, Claude ; Rao, D. C. / Evidence for at least two major loci influencing human fatness. In: American Journal of Human Genetics. 1998 ; Vol. 63, No. 3. pp. 831-838.
@article{a2c541caea4e4a99b2289b99e3070245,
title = "Evidence for at least two major loci influencing human fatness",
abstract = "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.",
author = "Borecki, {Ingrid B.} and John Blangero and Treva Rice and Louis P{\'e}russe and Claude Bouchard and Rao, {D. C.}",
year = "1998",
month = "9",
doi = "10.1086/302006",
language = "English (US)",
volume = "63",
pages = "831--838",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "3",

}

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.

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

UR - http://www.scopus.com/inward/citedby.url?scp=0032231716&partnerID=8YFLogxK

U2 - 10.1086/302006

DO - 10.1086/302006

M3 - Article

C2 - 9718336

AN - SCOPUS:0032231716

VL - 63

SP - 831

EP - 838

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

IS - 3

ER -