Sex-specific genetic architecture of human fatness in Chinese: the SAPPHIRe Study.
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.
Chiu
Y-F
YF
Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, 35 Keyan Rd, Zhunan, Miaoli 350, Taiwan, ROC.
Chuang
L-M
LM
Kao
H-Y
HY
Shih
K-C
KC
Lin
M-W
MW
Lee
W-J
WJ
Quertermous
T
T
Curb
J D
JD
Chen
I
I
Rodriguez
B L
BL
Hsiung
C A
CA
D000328:Adult; D044466:Asian People / Q000235:genetics*; D015992:Body Mass Index; D002874:Chromosome Mapping; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006254:Hawaii / Q000453:epidemiology; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology / Q000235:genetics*; D016017:Odds Ratio; D010641:Phenotype; D012495:San Francisco / Q000453:epidemiology; D012727:Sex Characteristics; D012737:Sex Factors; D013624:Taiwan / Q000453:epidemiology