Tests of linkage and/or association of the LEPR gene polymorphisms with obesity phenotypes in Caucasian nuclear families

Yong Jun Liu, Sonia Rocha-Sanchez, Peng Yuan Liu, Ji Rong Long, Yan Lu, Leo Elze, Robert R. Recker, Hong Wen Deng

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Abstract

Genetic variations in the leptin receptor (LEPR) gene have been conceived to affect body weight in general populations. In this study, using the tests implemented in the statistical package QTDT, we evaluated association and/or linkage of the LEPR gene with obesity phenotypes in a large sample comprising 1,873 subjects from 405 Caucasian nuclear families. Obesity phenotypes tested include body mass index (BMI), fat mass, percentage fat mass (PFM), and lean mass, with the latter three measured by dual-energy X-ray absorptiometry (DXA). Three single nucleotide polymorphisms (SNPs), namely Lys109Arg (MG), Lys656Asn (G/C), Pro1019Pro (G/A), in the LEPR gene were analyzed. Significant linkage disequilibrium (0.394 ≤ |D′| ≤ 0.688, P <0.001) was observed between pairs of the three SNPs. No significant population stratification was found for any SNP/phenotype. In single-locus analyses, evidence of association was observed for Lys656Asn with lean mass (P = 0.002) and fat mass (P = 0.015). The contribution of this polymorphism to the phenotypic variation of lean mass and fat mass was 2.63% and 1.15%, respectively. Subjects carrying allele G at the Lys656Asn site had, on average, 3.16% higher lean mass and 2.71% higher fat mass than those without it. In the analyses for haplotypes defined by the three SNPs, significant associations were detected between haplotype GCA (P = 0.005) and lean mass. In addition, marginally significant evidence of association was observed for this haplotype with fat mass (P = 0.012). No statistically significant linkage was found, largely due to the limited power of the linkage approach to detect small genetic effects in our data sets. Our results suggest that the LEPR gene polymorphisms contribute to variation in obesity phenotypes.

Original languageEnglish
Pages (from-to)101-106
Number of pages6
JournalPhysiological Genomics
Volume17
DOIs
StatePublished - Jul 2004

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Leptin Receptors
Nuclear Family
Obesity
Fats
Phenotype
Single Nucleotide Polymorphism
Haplotypes
Genes
Linkage Disequilibrium
Photon Absorptiometry
Population
Body Mass Index
Alleles
Body Weight

All Science Journal Classification (ASJC) codes

  • Physiology
  • Genetics

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Tests of linkage and/or association of the LEPR gene polymorphisms with obesity phenotypes in Caucasian nuclear families. / Liu, Yong Jun; Rocha-Sanchez, Sonia; Liu, Peng Yuan; Long, Ji Rong; Lu, Yan; Elze, Leo; Recker, Robert R.; Deng, Hong Wen.

In: Physiological Genomics, Vol. 17, 07.2004, p. 101-106.

Research output: Contribution to journalArticle

Liu, Yong Jun ; Rocha-Sanchez, Sonia ; Liu, Peng Yuan ; Long, Ji Rong ; Lu, Yan ; Elze, Leo ; Recker, Robert R. ; Deng, Hong Wen. / Tests of linkage and/or association of the LEPR gene polymorphisms with obesity phenotypes in Caucasian nuclear families. In: Physiological Genomics. 2004 ; Vol. 17. pp. 101-106.
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abstract = "Genetic variations in the leptin receptor (LEPR) gene have been conceived to affect body weight in general populations. In this study, using the tests implemented in the statistical package QTDT, we evaluated association and/or linkage of the LEPR gene with obesity phenotypes in a large sample comprising 1,873 subjects from 405 Caucasian nuclear families. Obesity phenotypes tested include body mass index (BMI), fat mass, percentage fat mass (PFM), and lean mass, with the latter three measured by dual-energy X-ray absorptiometry (DXA). Three single nucleotide polymorphisms (SNPs), namely Lys109Arg (MG), Lys656Asn (G/C), Pro1019Pro (G/A), in the LEPR gene were analyzed. Significant linkage disequilibrium (0.394 ≤ |D′| ≤ 0.688, P <0.001) was observed between pairs of the three SNPs. No significant population stratification was found for any SNP/phenotype. In single-locus analyses, evidence of association was observed for Lys656Asn with lean mass (P = 0.002) and fat mass (P = 0.015). The contribution of this polymorphism to the phenotypic variation of lean mass and fat mass was 2.63{\%} and 1.15{\%}, respectively. Subjects carrying allele G at the Lys656Asn site had, on average, 3.16{\%} higher lean mass and 2.71{\%} higher fat mass than those without it. In the analyses for haplotypes defined by the three SNPs, significant associations were detected between haplotype GCA (P = 0.005) and lean mass. In addition, marginally significant evidence of association was observed for this haplotype with fat mass (P = 0.012). No statistically significant linkage was found, largely due to the limited power of the linkage approach to detect small genetic effects in our data sets. Our results suggest that the LEPR gene polymorphisms contribute to variation in obesity phenotypes.",
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