TY - JOUR
T1 - Sex-specific findings from a genome-wide linkage analysis of human fatness in non-Hispanic whites and African Americans
T2 - The HyperGEN Study
AU - Lewis, C. E.
AU - North, K. E.
AU - Arnett, D.
AU - Borecki, I. B.
AU - Coon, H.
AU - Ellison, R. C.
AU - Hunt, S. C.
AU - Oberman, A.
AU - Rich, S. S.
AU - Province, M. A.
AU - Miller, M. B.
PY - 2005/6
Y1 - 2005/6
N2 - 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 chromosomel 2q (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 Africa-America 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.
AB - 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 chromosomel 2q (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 Africa-America 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.
KW - Body composition
KW - Body mass index
KW - Linkage (genetic)
UR - https://www.scopus.com/pages/publications/20144380431
U2 - 10.1038/sj.ijo.0802916
DO - 10.1038/sj.ijo.0802916
M3 - Article
C2 - 15809668
AN - SCOPUS:20144380431
SN - 0307-0565
VL - 29
SP - 639
EP - 649
JO - International Journal of Obesity
JF - International Journal of Obesity
IS - 6
ER -