Linkage analysis of factors underlying insulin resistance: Strong Heart Family Study.
In previous work in non-diabetic participants of the Strong Heart Family Study, we identified three heritable principal components of nine insulin resistance (IR) phenotypes: 1) a glucose/insulin/obesity factor, 2) a blood pressure factor, and 3) a dyslipidemia factor. To localize quantitative trait loci (QTL) potentially influencing these factors, we conducted a genome scan of factor scores in Strong Heart Family Study participants. Approximately 599 men and women, >or=18 years of age, in 32 extended families at three centers (in Arizona, Oklahoma, and North and South Dakota), were examined between 1997 and 1999. We used variance components linkage analysis to identify QTLs for the IR factors. With age, sex, and study center as covariates, we detected linkage of the glucose/insulin/obesity factor to chromosome 4 (robust logarithm of the odds (LOD) = 2.2), the dyslipidemia factor to chromosome 12 (robust LOD = 2.7), and the blood pressure factor to chromosome 1 (robust LOD = 1.6). The peak linkage signals identified for these IR factors support several positive findings from other studies and occur in regions harboring interesting candidate genes. The corroboration of existing QTLs will bring us closer to the identification of the functional genes that predispose to IR.
North
Kari E
KE
Department of Epidemiology, University of North Carolina, Chapel Hill, Bank of America Center, 137 E. Franklin Street, Suite 306, NC 27514, USA. kari_north@unc.edu
Almasy
Laura
L
Göring
Harald H H
HH
Cole
Shelley A
SA
Diego
Vincent P
VP
Laston
Sandra
S
Cantu
Teresa
T
Williams
Jeff T
JT
Howard
Barbara V
BV
Lee
Elisa T
ET
Best
Lyle G
LG
Fabsitz
Richard R
RR
MacCluer
Jean W
JW
D000368:Aged; D001786:Blood Glucose / Q000235:genetics; D001794:Blood Pressure / Q000235:genetics; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D015331:Cohort Studies; D050171:Dyslipidemias / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006331:Heart Diseases / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D007198:Indians, North American / Q000235:genetics; D007328:Insulin / Q000235:genetics; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics; D010641:Phenotype; D040641:Quantitative Trait Loci
D001786:Blood Glucose; D007328:Insulin