A major quantitative trait locus determining serum leptin levels and fat mass is located on human chromosome 2

Anthony G. Comuzzie, James E. Hixson, Laura Almasy, Braxton D. Mitchell, Michael C. Mahaney, Thomas D. Dyer, Michael P. Stern, Jean W. MacCluer, John Blangero

Research output: Contribution to journalArticle

405 Citations (Scopus)

Abstract

Obesity is a major predisposing factor for the development of several chronic diseases including non-insulin dependent diabetes mellitus (NIDDM) and coronary heart disease (CHD). Leptin is a serum protein which is secreted by adipocytes and thought to play a role in the regulation of body fat. Leptin levels in humans have been found to be highly correlated with an individual's total adiposity. We performed a genome-wide scan and conducted multipoint linkage analysis using a general pedigree-based variance component approach to identify genes with measurable effects on quantitative variation in leptin levels in Mexican Americans. A microsatellite polymorphism, D2S1788, mapped to chromosome 2p21 (approximately 74 cM from the tip of the short arm) and showed strong evidence of linkage with serum leptin levels with a lod score of 4.95 (P = 9 x 10-7). This locus accounted for 47% of the variation in serum leptin levels, with a residual additive genetic component contributing an additional 24%. This region contains several potential candidate genes for obesity, including glucokinase regulatory protein (GCKR) end pro-opiomelanocortin (POMC). Our results show strong evidence of linkage of this region of chromosome 2 with serum leptin levels and indicate that this region could contain an important human obesity gene.

Original languageEnglish (US)
Pages (from-to)273-276
Number of pages4
JournalNature Genetics
Volume15
Issue number3
DOIs
StatePublished - Mar 1997
Externally publishedYes

Fingerprint

Chromosomes, Human, Pair 2
Quantitative Trait Loci
Human Chromosomes
Leptin
Fats
Serum
Obesity
Genes
Lod Score
Pro-Opiomelanocortin
Adiposity
Pedigree
Adipocytes
Causality
Microsatellite Repeats
Type 2 Diabetes Mellitus
Coronary Disease
Adipose Tissue
Blood Proteins
Chronic Disease

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Comuzzie, A. G., Hixson, J. E., Almasy, L., Mitchell, B. D., Mahaney, M. C., Dyer, T. D., ... Blangero, J. (1997). A major quantitative trait locus determining serum leptin levels and fat mass is located on human chromosome 2. Nature Genetics, 15(3), 273-276. https://doi.org/10.1038/ng0397-273

A major quantitative trait locus determining serum leptin levels and fat mass is located on human chromosome 2. / Comuzzie, Anthony G.; Hixson, James E.; Almasy, Laura; Mitchell, Braxton D.; Mahaney, Michael C.; Dyer, Thomas D.; Stern, Michael P.; MacCluer, Jean W.; Blangero, John.

In: Nature Genetics, Vol. 15, No. 3, 03.1997, p. 273-276.

Research output: Contribution to journalArticle

Comuzzie, AG, Hixson, JE, Almasy, L, Mitchell, BD, Mahaney, MC, Dyer, TD, Stern, MP, MacCluer, JW & Blangero, J 1997, 'A major quantitative trait locus determining serum leptin levels and fat mass is located on human chromosome 2', Nature Genetics, vol. 15, no. 3, pp. 273-276. https://doi.org/10.1038/ng0397-273
Comuzzie, Anthony G. ; Hixson, James E. ; Almasy, Laura ; Mitchell, Braxton D. ; Mahaney, Michael C. ; Dyer, Thomas D. ; Stern, Michael P. ; MacCluer, Jean W. ; Blangero, John. / A major quantitative trait locus determining serum leptin levels and fat mass is located on human chromosome 2. In: Nature Genetics. 1997 ; Vol. 15, No. 3. pp. 273-276.
@article{a5f30c9f61ca4d8dae7ec47bcf8c752c,
title = "A major quantitative trait locus determining serum leptin levels and fat mass is located on human chromosome 2",
abstract = "Obesity is a major predisposing factor for the development of several chronic diseases including non-insulin dependent diabetes mellitus (NIDDM) and coronary heart disease (CHD). Leptin is a serum protein which is secreted by adipocytes and thought to play a role in the regulation of body fat. Leptin levels in humans have been found to be highly correlated with an individual's total adiposity. We performed a genome-wide scan and conducted multipoint linkage analysis using a general pedigree-based variance component approach to identify genes with measurable effects on quantitative variation in leptin levels in Mexican Americans. A microsatellite polymorphism, D2S1788, mapped to chromosome 2p21 (approximately 74 cM from the tip of the short arm) and showed strong evidence of linkage with serum leptin levels with a lod score of 4.95 (P = 9 x 10-7). This locus accounted for 47{\%} of the variation in serum leptin levels, with a residual additive genetic component contributing an additional 24{\%}. This region contains several potential candidate genes for obesity, including glucokinase regulatory protein (GCKR) end pro-opiomelanocortin (POMC). Our results show strong evidence of linkage of this region of chromosome 2 with serum leptin levels and indicate that this region could contain an important human obesity gene.",
author = "Comuzzie, {Anthony G.} and Hixson, {James E.} and Laura Almasy and Mitchell, {Braxton D.} and Mahaney, {Michael C.} and Dyer, {Thomas D.} and Stern, {Michael P.} and MacCluer, {Jean W.} and John Blangero",
year = "1997",
month = "3",
doi = "10.1038/ng0397-273",
language = "English (US)",
volume = "15",
pages = "273--276",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "3",

}

TY - JOUR

T1 - A major quantitative trait locus determining serum leptin levels and fat mass is located on human chromosome 2

AU - Comuzzie, Anthony G.

AU - Hixson, James E.

AU - Almasy, Laura

AU - Mitchell, Braxton D.

AU - Mahaney, Michael C.

AU - Dyer, Thomas D.

AU - Stern, Michael P.

AU - MacCluer, Jean W.

AU - Blangero, John

PY - 1997/3

Y1 - 1997/3

N2 - Obesity is a major predisposing factor for the development of several chronic diseases including non-insulin dependent diabetes mellitus (NIDDM) and coronary heart disease (CHD). Leptin is a serum protein which is secreted by adipocytes and thought to play a role in the regulation of body fat. Leptin levels in humans have been found to be highly correlated with an individual's total adiposity. We performed a genome-wide scan and conducted multipoint linkage analysis using a general pedigree-based variance component approach to identify genes with measurable effects on quantitative variation in leptin levels in Mexican Americans. A microsatellite polymorphism, D2S1788, mapped to chromosome 2p21 (approximately 74 cM from the tip of the short arm) and showed strong evidence of linkage with serum leptin levels with a lod score of 4.95 (P = 9 x 10-7). This locus accounted for 47% of the variation in serum leptin levels, with a residual additive genetic component contributing an additional 24%. This region contains several potential candidate genes for obesity, including glucokinase regulatory protein (GCKR) end pro-opiomelanocortin (POMC). Our results show strong evidence of linkage of this region of chromosome 2 with serum leptin levels and indicate that this region could contain an important human obesity gene.

AB - Obesity is a major predisposing factor for the development of several chronic diseases including non-insulin dependent diabetes mellitus (NIDDM) and coronary heart disease (CHD). Leptin is a serum protein which is secreted by adipocytes and thought to play a role in the regulation of body fat. Leptin levels in humans have been found to be highly correlated with an individual's total adiposity. We performed a genome-wide scan and conducted multipoint linkage analysis using a general pedigree-based variance component approach to identify genes with measurable effects on quantitative variation in leptin levels in Mexican Americans. A microsatellite polymorphism, D2S1788, mapped to chromosome 2p21 (approximately 74 cM from the tip of the short arm) and showed strong evidence of linkage with serum leptin levels with a lod score of 4.95 (P = 9 x 10-7). This locus accounted for 47% of the variation in serum leptin levels, with a residual additive genetic component contributing an additional 24%. This region contains several potential candidate genes for obesity, including glucokinase regulatory protein (GCKR) end pro-opiomelanocortin (POMC). Our results show strong evidence of linkage of this region of chromosome 2 with serum leptin levels and indicate that this region could contain an important human obesity gene.

UR - http://www.scopus.com/inward/record.url?scp=0031017322&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031017322&partnerID=8YFLogxK

U2 - 10.1038/ng0397-273

DO - 10.1038/ng0397-273

M3 - Article

C2 - 9054940

AN - SCOPUS:0031017322

VL - 15

SP - 273

EP - 276

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 3

ER -