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Human Molecular Genetics Advance Access originally published online on April 12, 2006
Human Molecular Genetics 2006 15(10):1569-1579; doi:10.1093/hmg/ddl076
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© The Author 2006. Published by Oxford University Press. All rights reserved.
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A quantitative trait locus (QTL) on chromosome 6q influences birth weight in two independent family studies

Rector Arya1,4,*, Ellen Demerath5, Christopher P. Jenkinson2, Harald H.H. Göring4, Sobha Puppala4, Vidya Farook4, Sharon Fowler1, Jennifer Schneider4, Richard Granato1, Roy G. Resendez4, Thomas D. Dyer4, Shelley A. Cole4, Laura Almasy4, Anthony G. Comuzzie4, Roger M. Siervogel5, Benjamin Bradshaw3, Ralph A. DeFronzo2, Jean MacCluer4, Michael P. Stern1, Bradford Towne5, John Blangero4 and Ravindranath Duggirala4

1Division of Clinical Epidemiology, 2Division of Diabetes, Department of Medicine and 3School of Public Health, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA, 4Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX 78245, USA and 5The Wright State University School of Medicine, Kettering, OH 45420, USA

* To whom correspondence should be addressed. Tel: +1 2105675234; Fax: +1 2105676955; Email: arya{at}uthscsa.edu

Received January 25, 2006; Accepted March 22, 2006

Low birth weight is an important cause of infant mortality and morbidity worldwide. Birth weight has been shown to be inversely correlated with adult complex diseases such as obesity, type-2 diabetes and cardiovascular disease. However, little is known about the genetic factors influencing variation in birth weight and its association with diseases that occur in later life. We, therefore, have performed a genome-wide search to identify genes that influence birth weight in Mexican-Americans using the data from the San Antonio Family Birth Weight Study participants (n=840). Heritability of birth weight was estimated as 72.0±8.4% (P<0.0001) after adjusting for the effects of sex and term. Multipoint linkage analysis yielded the strongest evidence for linkage of birth weight (LOD=3.7) between the markers D6S1053 and D6S1031 on chromosome 6q. This finding has been replicated (LOD=2.3) in an independent European-American population. Together, these findings provide substantial evidence (LODadj=4.3) for a major locus influencing variation in birth weight. This region harbors positional candidate genes such as chorionic gonadotropin, alpha chain; collagen, type XIX, alpha-1; and protein-tyrosine phosphatase, type 4A, 1 that may play a role in fetal growth and development. In addition, potential evidence for linkage (LOD≥1.2) was found on chromosomes 1q, 2q, 3q, 4q, 9p, 19p and 19q with LODs ranging from 1.3 to 2.7. Thus, we have found strong evidence for a major gene on chromosome 6q that influences variation in birth weight in both Mexican- and European-Americans.


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