Sex-specific genetic architecture of human fatness in Chinese: The SAPPHIRe Study
Journal
Human Genetics
Journal Volume
128
Journal Issue
5
Pages
501-513
Date Issued
2010
Author(s)
Chiu Y.-F.
Kao H.-Y.
Shih K.-C.
Lin M.-W.
Lee W.-J.
Quertermous T.
Curb J.D.
Chen I.
Rodriguez B.L.
Hsiung C.A.
Abstract
To dissect the genetic architecture of sexual dimorphism in obesity-related traits, we evaluated the sex-genotype interaction, sex-specific heritability and genome-wide linkages for seven measurements related to obesity. A total of 1,365 non-diabetic Chinese subjects from the family study of the Stanford Asia-Pacific Program of Hypertension and Insulin Resistance were used to search for quantitative trait loci (QTLs) responsible for the obesity-related traits. Pleiotropy and co-incidence effects from the QTLs were also examined using the bivariate linkage approach. We found that sex-specific differences in heritability and the genotype-sex interaction effects were substantially significant for most of these traits. Several QTLs with strong linkage evidence were identified after incorporating genotype by sex (G × S) interactions into the linkage mapping, including one QTL for hip circumference [maximum LOD score (MLS) = 4.22, empirical p = 0.000033] and two QTLs: for BMI on chromosome 12q with MLS 3.37 (empirical p = 0.0043) and 3.10 (empirical p = 0.0054). Sex-specific analyses demonstrated that these linkage signals all resulted from females rather than males. Most of these QTLs for obesity-related traits replicated the findings in other ethnic groups. Bivariate linkage analyses showed several obesity traits were influenced by a common set of QTLs. All regions with linkage signals were observed in one gender, but not in the whole sample, suggesting the genetic architecture of obesity-related traits does differ by gender. These findings are useful for further identification of the liability genes for these phenotypes through candidate genes or genome-wide association analysis. ? 2010 Springer-Verlag.
SDGs
Other Subjects
adult; article; bivariate analysis; body mass; Chinese; chromosome 12q; female; gene mapping; genetic association; genetic linkage; genotype; heritability; human; major clinical study; male; obesity; pleiotropy; priority journal; quantitative trait locus; sex difference; waist hip ratio; Asian; chromosome map; genetics; middle aged; obesity; phenotype; risk; sex difference; sexual development; Taiwan; United States; Adult; Asian Continental Ancestry Group; Body Mass Index; Chromosome Mapping; Female; Genome-Wide Association Study; Genotype; Hawaii; Humans; Lod Score; Male; Middle Aged; Obesity; Odds Ratio; Phenotype; San Francisco; Sex Characteristics; Sex Factors; Taiwan
Type
journal article