A study of linkage and association of body mass index in the Old Order Amish

Petra Platte, George J. Papanicolaou, Jennifer J. Johnston, Claudia M. Klein, Kimberly F. Doheny, Elizabeth W. Pugh, Marie Helene Roy-Gagnon, Albert J. Stunkard, Clair A. Francomano, Alexander F. Wilson

Research output: Contribution to journalArticle

Abstract

Obesity is thought to have a genetic component with the estimates of heritability ranging from 0.25-0.40. As part of an ongoing study of obesity in the Old Order Amish, seven two- and three-generation families (157 individuals) were assessed for 21 traits related to obesity, including body mass index (BMI) and BMI-percentile (a standardized distribution of BMI adjusted for age and sex). Genotyping was performed using a panel of 384 short-tandem repeat markers. In this sample, the estimates of heritability ranged from 0.16-0.31 for BMI and from 0.40-0.52 for BMI-percentile. Model-independent linkage analysis identified candidate regions on chromosomes 1, 5, 7, 8, and 11. Given that several markers on 7q were significant for both BMI and BMI-percentile (P ≤ 0.001) and that the structural locus for leptin was located on 7q, this region was considered to be the primary candidate region. Subsequent typing of additional flanking markers on 7q corroborated the original findings. Tests of intrafamilial association for alleles at markers in this candidate region were significant at similar levels. Although there is some evidence for linkage and association in the region containing leptin, there appears to be stronger evidence for linkage (P ≤ 0.001) and association (P ≤ 0.00001) with BMI in a region 10-15 cM further downstream of leptin, flanked by markers D7S1804 and D7S3070 with peak values from D7S495-D7S1798. Evidence from linkage and association studies suggests that this region (D7S1804-D7S3070) maybe responsible, at least in part, for variation in BMI and BMI-percentile in the Old Order Amish.

Original languageEnglish (US)
Pages (from-to)71-80
Number of pages10
JournalAmerican Journal of Medical Genetics - Seminars in Medical Genetics
Volume121 C
Issue number1
DOIs
StatePublished - Aug 15 2003

Keywords

  • Association
  • Body mass index
  • Linkage

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Platte, P., Papanicolaou, G. J., Johnston, J. J., Klein, C. M., Doheny, K. F., Pugh, E. W., Roy-Gagnon, M. H., Stunkard, A. J., Francomano, C. A., & Wilson, A. F. (2003). A study of linkage and association of body mass index in the Old Order Amish. American Journal of Medical Genetics - Seminars in Medical Genetics, 121 C(1), 71-80. https://doi.org/10.1002/ajmg.c.20005