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Human Molecular Genetics Advance Access published online on April 12, 2006
Human Molecular Genetics, doi:10.1093/hmg/ddl076
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© The Author 2006. Published by Oxford University Press. All rights reserved. The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oupjournals.org
Received January 25, 2006
Revised March 22, 2006
Accepted March 22, 2006

Article

A Quantitative Trait Locus (QTL) on Chromosome 6q Influences Birth Weight in Two Independent Family Studies

Rector Arya Ph.D. 1 *, Ellen Demerath 2, Christopher P. Jenkinson 3, Harald HH Göring 4, Sobha Puppala 4, Vidya Farook 4, Sharon Fowler 5, Jennifer Schneider 4, Richard Granato 5, Roy G. Resendez 4, Thomas D. Dyer 4, Shelley A. Cole 4, Laura Almasy 4, Anthony G. Comuzzie 4, Roger M. Siervogel 2, Benjamin Bradshaw 6, Ralph A. DeFronzo 3, Jean MacCluer 4, Michael P. Stern 5, Bradford Towne 2, John Blangero 4, and Ravindranath Duggirala 4

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

* To whom correspondence should be addressed.
Rector Arya, E-mail: arya{at}uthscsa.edu


  Abstract

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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