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Sex-specific findings from a genome-wide linkage analysis of human fatness in non-Hispanic whites and African Americans: The HyperGEN Study

International Journal of Obesity volume 29, pages 639–649 (2005)Cite this article

Abstract

OBJECTIVE:

To conduct a full genome search for genes potentially influencing two related phenotypes: body mass index (BMI, kg/m2) and percent body fat (PBF) from bioelectric impedance in men and women.

DESIGN:

A total of 3383 participants, 1348 men and 2035 women; recruitment was initiated with hypertensive sibpairs and expanded to first-degree relatives in a multicenter study of hypertension genetics.

MEASUREMENTS:

Genotypes for 387 highly polymorphic markers spaced to provide a 10 cM map (CHLC-8) were generated by the NHLBI Mammalian Genotyping Service (Marshfield, WI, USA). Quantitative trait loci for obesity phenotypes, BMI and PBF, were examined with a variance components method using SOLAR, adjusting for hypertensive status, ethnicity, center, age, age2, sex, and age2 × sex. As we detected a significant genotype-by-sex interaction in initial models and because of the importance of sex effects in the expression of these phenotypes, models thereafter were stratified by sex. No genotype-by-ethnicity interactions were found.

RESULTS:

A QTL influencing PBF in women was detected on chromosome12q (12q24.3–12q24.32, maximum empirical LOD score=3.8); a QTL influencing this phenotype in men was found on chromosome 15q (15q25.3, maximum empirical LOD score=3.0). These QTLs were detected in African-American and white women (12q) and men (15q). QTLs influencing both BMI and PBF were found over a broad region on chromosome 3 in men. QTLs on chromosomes 3 and 12 were found in the combined sample of men and women, but with weaker significance.

CONCLUSION:

The locations with highest LOD scores have been previously reported for obesity phenotypes, indicating that at least two genomic regions influence obesity-related traits. Furthermore, our results indicate the importance of considering context-dependent effects in the search for obesity QTLs.

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Acknowledgements

HyperGEN Primary Centers and Investigators—University of Utah (Network Coordinating Center, Field Center, and Molecular Genetics Lab): Steven C Hunt, PhD (Network Director and Field Center PI); Mark F Leppert, PhD (Molecular Genetics PI); Jean-Marc Lalouel, MD, DSc; Robert B Weiss, PhD; Paul N Hopkins, MD, MSPH; Hilary Coon, PhD; Roger R Williams, MD (late); Janet Hood; Jan K Skuppin. Boston University (Field Center): R Curtis Ellison, MD (PI); Richard H Myers, PhD; Luc Djoussé, MD, DSc; Yuqing Zhang, MD; Jemma B Wilk, DSc; Greta Lee Splansky, MS. University of Alabama (Field Center): Albert Oberman, MD, MPH (PI); Cora E Lewis, MD, MSPH; Michael T Weaver, PhD; Phillip Johnson; Susan Walker; Christie Oden. University of Minnesota (Field Center and Biochemistry Lab): Donna K Arnett, PhD (Field Center PI); John H Eckfeldt, MD, PhD (Biochemistry Lab PI); James S Pankow, PhD; Michael B Miller, PhD; Anthony A Killeen, MD, PhD; Kim Weis, MPH; Greg Rynders; Catherine Leiendecker-Foster, MS; Gregory Feitl; Barbara Lux; Jean Bucksa. University of North Carolina (Field Center): Gerardo Heiss, MD, PhD (PI); Barry I Freedman, MD; Kari E North, PhD; Kathryn Rose, PhD; Amy Haire. Washington University (Data Coordinating Center): DC Rao, PhD (PI); Michael A Province, PhD; Aldi Kraja, PhD; Ingrid B Borecki, PhD; Charles Gu, PhD; Treva Rice, PhD; Mary Feitosa, PhD; Jun Wu, MD; Karen L Schwander, MS; Derek Morgan; Stephen Mandel; Shiping Wang MS; Brandon Pierce; David J Lehner. National Heart, Lung and Blood Institute: Susan E Old, PhD; Cashell Jaquish, PhD; Dina Paltoo, PhD. This hypertension network is funded by cooperative agreements (U10) with NHLBI: HL54471, HL54472, HL-54473, HL54495, HL54496, HL54497, HL54509, HL54515.

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Authors and Affiliations

  1. Division of Preventive Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA

    C E Lewis & A Oberman

  2. Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA

    K E North

  3. Division of Epidemiology, University of Minnesota, Minneapolis, MN, USA

    D Arnett & M B Miller

  4. Division of Biostatistics, Department of Genetics, Washington University School of Medicine, St Louis, MO, USA

    I B Borecki & M A Province

  5. Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT, USA

    H Coon

  6. Section of Preventive Medicine and Epidemiology, Boston University School of Medicine, Boston, MA, USA

    R C Ellison

  7. Cardiovascular Genetics Research Clinic, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA

    S C Hunt

  8. Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA

    S S Rich

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  1. C E Lewis
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  2. K E North
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  3. D Arnett
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  4. I B Borecki
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  5. H Coon
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  6. R C Ellison
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  7. S C Hunt
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  8. A Oberman
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  9. S S Rich
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  10. M A Province
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  11. M B Miller
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Correspondence to C E Lewis.

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Lewis, C., North, K., Arnett, D. et al. Sex-specific findings from a genome-wide linkage analysis of human fatness in non-Hispanic whites and African Americans: The HyperGEN Study. Int J Obes 29, 639–649 (2005). https://doi.org/10.1038/sj.ijo.0802916

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  • DOI: https://doi.org/10.1038/sj.ijo.0802916

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