title: Genotype-by-sex interaction on fasting insulin concentration: the HyperGEN study.
abstract: Recent studies have demonstrated the importance of sex effects on the underlying genetic architecture of insulin-related traits. To explore sex-specific genetic effects on fasting insulin, we tested for genotype-by-sex interaction and conducted linkage analysis of fasting insulin in Hypertension Genetic Epidemiology Network families. Hypertensive siblings and their first-degree relatives were recruited from five field centers. We performed a genome scan for quantitative trait loci influencing fasting insulin among 1,505 European Americans and 1,616 African Americans without diabetes. Sex-stratified linear regression models, adjusted for race, center, and age, were explored. The Mammalian Genotyping Service typed 391 microsatellite markers, spaced roughly 9 cM. Variance component linkage analysis was performed in SOLAR using ethnic-specific marker allele frequencies and multipoint IBDs calculated in MERLIN. We detected a quantitative trait locus influencing fasting insulin in female subjects (logarithm of odds [LOD] = 3.4) on chromosome 2 at 95 cM (between GATA69E12 and GATA71G04) but not in male subjects (LOD = 0.0, P for interaction = 0.007). This sex-specific signal at 2p13.2 was detected in both European-American (LOD = 2.1) and African-American (LOD = 1.2) female subjects. Our findings overlap with several other linkage reports of insulin-related traits and demonstrate the importance of considering complex context-dependent interactions in the search for insulin-related genes.
authors.affiliation: Department of Epidemiology, University of North Carolina Chapel Hill, Bank of America Center, 137 E. Franklin St., Suite 306, Chapel Hill, NC 27514, USA. kari_north@unc.edu
authors.forename: Kari E
authors.initials: KE
authors.lastname: North
authors.forename: Nora
authors.initials: N
authors.lastname: Franceschini
authors.forename: Ingrid B
authors.initials: IB
authors.lastname: Borecki
authors.forename: C Charles
authors.initials: CC
authors.lastname: Gu
authors.forename: Gerardo
authors.initials: G
authors.lastname: Heiss
authors.forename: Michael A
authors.initials: MA
authors.lastname: Province
authors.forename: Donna K
authors.initials: DK
authors.lastname: Arnett
authors.forename: Cora E
authors.initials: CE
authors.lastname: Lewis
authors.forename: Michael B
authors.initials: MB
authors.lastname: Miller
authors.forename: Richard H
authors.initials: RH
authors.lastname: Myers
authors.forename: Steven C
authors.initials: SC
authors.lastname: Hunt
authors.forename: Barry I
authors.initials: BI
authors.lastname: Freedman
mesh_terms: D000428:Alcohol Drinking; D005215:Fasting; D005260:Female; D005838:Genotype; D006801:Humans; D007328:Insulin / Q000097:blood* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012727:Sex Characteristics; D012907:Smoking / Q000453:epidemiology
chemical_list: D007328:Insulin