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Diabetes 51:848-855, 2002
© 2002 by the American Diabetes Association, Inc.

A Genomewide Linkage Scan for Abdominal Subcutaneous and Visceral Fat in Black and White Families

The HERITAGE Family Study

Treva Rice1, Yvon C. Chagnon4, Louis Pérusse5, Ingrid B. Borecki1,2, Olavi Ukkola7,8, Tuomo Rankinen8, Jacques Gagnon6, Arthur S. Leon9, James S. Skinner10, Jack H. Wilmore11, Claude Bouchard8, and D.C. Rao1,2,3

1 Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri
2 Department of Genetics, Washington University School of Medicine, St. Louis, Missouri
3 Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri
4 Physical Activity Sciences Laboratory, Laval University, Québec, Canada
5 Division of Kinesiology and Department of Preventive Medicine, Laval University, Québec, Canada
6 Molecular Endocrinology Laboratory, Laval University, Québec, Canada
7 Department of Internal Medicine and Biocenter Oulu, University of Oulu, Oulu, Finland
8 Pennington Biomedical Research Center, Baton Rouge, LA
9 School of Kinesiology and Leisure Studies, University of Minnesota, Minneapolis, Minnesota
10 Division of Kinesiology, Indiana University, Bloomington, Indiana
11 Department of Health and Kinesiology, Texas A & M University, College Station, Texas

Abdominal visceral fat (AVF), abdominal subcutaneous fat (ASF), and abdominal total fat (ATF) were measured using a computed tomography scan, both before (baseline) and after (post) a 20-week endurance exercise training protocol in the HERITAGE Family Study. Each of the baseline and response (post minus baseline) measures was adjusted for several covariates, including total fat mass, and responses to training were further adjusted for baseline levels. Multipoint variance components linkage analysis using a genomewide scan of 344 markers was conducted separately by race using race-specific allele frequencies. Several promising results (P < 0.0023) were obtained. For baseline AVF, the best evidence was on 2q22.1 and 2q33.2-q36.3 (including the IRS1 locus) in whites, with suggestive findings on 7q22.2-q31.3 (including the LEP locus) in blacks. Although several regions were indicated for baseline ASF, only 4q31.22-q32.2 and 11p15.4-p11.2 replicated the results of another study. For responses to training, promising results were limited to ASF and ATF primarily on 7q36.2 (including NOS3) in blacks, with suggestive regions (P < 0.01) on 1q21.2-q24.1 (S100A, ATP1A2, and ATP1B1), 10q25.2 (ADRA2A), and 11p15.5 (IGF2). In summary, the 4q and 11p regions have now been implicated in two independent studies for ASF; further research is warranted to identify the genes and mutations in these regions that are responsible for fat accumulation in the abdominal depot. Additional work in an independent sample is needed to verify the linkages for baseline AVF as well as the response measures.


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