title: An autosomal genome-wide scan for loci linked to pre-diabetic phenotypes in nondiabetic Chinese subjects from the Stanford Asia-Pacific Program of Hypertension and Insulin Resistance Family Study.
abstract: Type 2 diabetes is a complex disease involving both genetic and environmental components. Abnormalities in insulin secretion and insulin action usually precede the development of type 2 diabetes and can serve as good quantitative measures for genetic mapping. We therefore undertook an autosomal genomic search to locate the quantitative trait locus (QTL) linked to these traits in 1,365 nondiabetic Chinese subjects from 411 nuclear families. Residuals of these log-transformed quantitative traits were analyzed in multipoint linkage analysis using a variance-components approach. The most significant QTL for fasting insulin, which coincides with the QTL for homeostasis model assessment of insulin resistance, was located at 37 cM on chromosome 20, with a maximum empirical logarithm of odds (LOD) score of 3.01 (empirical P = 0.00006) when adjusted for age, sex, BMI, antihypertensive medications, recruitment centers, and environmental factors. In the same region, a QTL for fasting glucose was identified at 51 cM, with an empirical LOD score of 2.03 (empirical P = 0.0012). There were other loci with maximum empirical LOD scores >or=1.29 located on chromosomes 1q, 2p, 5q, 7p, 9q, 10p, 14q, 18q, and 19q for different diabetes-related traits. These loci may harbor genes that regulate glucose homeostasis either independently or via interactions of the genes within these regions.
authors.affiliation: Division of BiostatisticsBioinformatics, National Health Research Institutes, Taipei, Taiwan.
authors.forename: Yen-Feng
authors.initials: YF
authors.lastname: Chiu
authors.forename: Lee-Ming
authors.initials: LM
authors.lastname: Chuang
authors.forename: Chin-Fu
authors.initials: CF
authors.lastname: Hsiao
authors.forename: Yi-Jen
authors.initials: YJ
authors.lastname: Hung
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Lin
authors.forename: Ying-Tsung
authors.initials: YT
authors.lastname: Chen
authors.forename: John
authors.initials: J
authors.lastname: Grove
authors.forename: Eric
authors.initials: E
authors.lastname: Jorgenson
authors.forename: Thomas
authors.initials: T
authors.lastname: Quertermous
authors.forename: Neil
authors.initials: N
authors.lastname: Risch
authors.forename: Chao A
authors.initials: CA
authors.lastname: Hsiung
mesh_terms: D044466:Asian People / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D005838:Genotype; D006254:Hawaii; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D010641:Phenotype; D011236:Prediabetic State / Q000208:ethnology / Q000235:genetics*; D040641:Quantitative Trait Loci; D012307:Risk Factors; D012495:San Francisco; D013624:Taiwan
chemical_list: D007328:Insulin