Genome-wide scans for heritability of fasting serum insulin and glucose concentrations in hypertensive families.
OBJECTIVE
The heritability of fasting serum insulin and glucose concentrations in non-diabetic members of multiplex hypertensive families is unknown.


METHODS
We calculated the familial aggregation of fasting serum glucose and insulin concentrations and performed a genome-wide scan to assess whether quantitative trait loci contribute to these phenotypes in 2,412 non-diabetic individuals from 1,030 families enrolled in the Hypertension Genetic Epidemiology Network (HyperGEN) in the Family Blood Pressure Program.


RESULTS
The heritability (+/-SE) of fasting serum insulin was 0.47+/-0.085 in European Americans and 0.28+/-0.08 in African Americans (p<0.0001 for both), after adjusting for age, sex, and BMI. A genome-wide scan for fasting serum insulin yielded a maximum log of the odds (LOD) score of 2.36 on chromosome 5 at 20 cM (p=0.0004) in European Americans, and an LOD score of 2.28 on chromosome 19 at 11 cM (p=0.0004) in African Americans. The heritability of fasting serum glucose was 0.5109+/-0.08 in the former and 0.29+/-0.09 in the latter (p<0.0003 for both) after adjusting for age, sex and BMI. A genome-wide scan for fasting serum glucose revealed a maximum LOD score of 2.07 on chromosome 5 at 26 cM (p=0.0009) in European Americans.


CONCLUSIONS
These analyses demonstrate the marked heritability of fasting serum insulin and glucose concentrations in families enriched for the presence of members with hypertension. They suggest that genes associated with fasting serum insulin concentration are present on chromosomes 19 and 5, and that genes associated with fasting serum glucose concentration are on chromosome 5, in families enriched for hypertension.
Freedman
B I
BI
Department of Internal Medicine, Section on Nephrology, The Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1053, USA. bfreedma@wfubmc.edu
Rich
S S
SS
Sale
M M
MM
Heiss
G
G
Djoussé
L
L
Pankow
J S
JS
Province
M A
MA
Rao
D C
DC
Lewis
C E
CE
Chen
Y D I
YD
Beck
S R
SR
D000328:Adult; D001741:Black or African American / Q000235:genetics; D000368:Aged; D000704:Analysis of Variance; D001786:Blood Glucose / Q000378:metabolism*; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D005192:Family Health; D005215:Fasting; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000235:genetics*; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D008390:Markov Chains; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D040641:Quantitative Trait Loci / Q000235:genetics*; D019655:Quantitative Trait, Heritable; D014481:United States; D044465:White People / Q000235:genetics
D001786:Blood Glucose; D007328:Insulin