Abstract for presentation at 11th International Congress of Human Genetics

Heritability of Brachymesophalangia-V and Related Phenotypes in an endogamous population from eastern Nepal

  • Kimberly Williams, Wright State University School of Medicine, Dayton, OH, United States
  • John Blangero, Southwest Foundation for Biomedical Research, San Antonio, TX, United States
  • Dana Duren, Wright State University School of Medicine, Dayton, OH, United States
  • C R Cottom, Wright State Unversity School of Medicine, United States
  • S Lawrence, Wright State University School of Medicine, United States
  • Thomas Dyer, Southwest Foundation for Biomedical Research, San Antonio, TX, United States
  • Janardan Subedi, Miami University, Oxford, OH, United States
  • B Jha, Tribhuvan University Institute of Medicine, Kathmandu, Nepal, Nepal
  • Sarah Williams-Blangero, Southwest Foundation for Biomedical Research, San Antonio, TX, United States
  • Bradford Towne, Wright State University School of Medicine, Dayton, OH, United States

    • Brachymesophalangia-V (BMP-V) is characterized by shortened length and increased breadth of the middle phalanx of the 5th digit. It is the most common of all hand anomalies, and is often seen as part of a suite of traits that characterize other brachydactylies, as well as certain diseases and disorders. Cone-shaped epiphyses (CE) are characterized by a projection from the epiphyseal plate extending toward the diaphysis of the bone. Cone-shaped epiphyses are commonly observed in conjunction with BMP-V. There may be a female bias in the prevalence of CE, although previous studies are not conclusive. Three potentially related phenotypes have been observed among children in the Jiri Growth Study, a genetic epidemiological study of child health conducted in the endogamous Jirel ethnic group of eastern Nepal. The Jirel population numbers approximately 5000, most of who are in one very large extended pedigree. A hand-wrist x-ray is taken annually of each child to assess skeletal development. X-rays of 1343 Jirel children (669 boys; 674 girls) were examined for presence or absence of BMP-V, BMP-V w/CE, and BMP-V either alone or in combination with CE. BMP-V was observed in 16.1% of the males and 13.1% of the females; BMP-V w/CE was observed in 6.4% of the males and 13.4% of the females; and either BMP-V or BMP-V w/CE was observed in 22.5% of the males and 26.5% of the females. A variance components-based method for pedigree data was used to estimate the heritability of these traits as an initial step in elucidating the genetic architecture of the BMP-V and CE phenotypes. The additive genetic heritabilities of these three traits are significant (BMP-V: h2= 0.66, p<0.001; BMP-V w/CE: h2= 0.54, p<0.001; BMP-V or CE: h2= 0.65, p<0.001). Furthermore, a significant sex bias was found for the CE phenotype (in conjunction with BMP-V) which supports previous studies suggesting a female bias in CE. Supported by NIH grants HD40377, AI37091, AI44406, and MH59490.

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