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

• Published in: International Journal of Obesity Vol. 29; no. 6; pp. 639 - 649
• Main Authors: LEWIS, C. E, NORTH, K. E, MILLER, M. B, ARNETT, D, BORECKI, I. B, COON, H, ELLISON, R. C, HUNT, S. C, OBERMAN, A, RICH, S. S, PROVINCE, M. A
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 01-06-2005; Nature Publishing Group
• Subjects: Adult; African Americans; Aged; Biological and medical sciences; Body Composition - genetics; Body Mass Index; Chromosomes; Chromosomes, Human, Pair 12; Chromosomes, Human, Pair 15; Chromosomes, Human, Pair 3; European Continental Ancestry Group; Female; Gene mapping; Genetics; Genotypes; Humans; Hypertension; Hypertension - ethnology; Hypertension - genetics; Hypertension - physiopathology; Impedance; Lod Score; Male; Mammals; Medical sciences; Metabolic diseases; Middle Aged; Obesity; Obesity - ethnology; Obesity - genetics; Obesity - physiopathology; Quantitative Trait Loci; Sex Factors; Human; Obesity; Nutrition disorder; Sex; linkage (genetic); Latinamerican; Fat mass; Body composition; Body mass index; White; Analysis; Genetic linkage; Genetics; Genome; Nutritional status; Public health; African American
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/sj.ijo.0802916

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.
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.
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 x 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.
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.
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.