A genome-wide search for genes affecting circulating fibrinogen levels in the Framingham Heart Study.
BACKGROUND
Circulating levels of fibrinogen are associated with atherosclerosis and predict future coronary heart disease and stroke. Levels of fibrinogen are correlated among family members, suggesting a heritable component. Variants of the beta-fibrinogen gene subunit on 4q28 are associated with fibrinogen levels but explain only a small proportion of the total genetic variability. It remains unknown what role, if any, is played by other genetic variants in the inter-individual variability in levels of fibrinogen in the general population.


METHODS
We conducted a 10-cM spaced genome-wide scan using 402 original cohort subjects and 1193 offspring subjects from 330 extended families of the Framingham Heart Study. Heritability and linkage analyses were carried out using variance component methods. Regression analyses were performed to adjust for traditional risk factors and HindIII beta-148 genotypes.


CONCLUSIONS
The total heritability was estimated as 0.24. The highest and second highest LOD scores of linkage were found on chromosomes 2 (LOD=1.5 at 243 cM) and 10 (LOD=2.4 at 87 cM) using only offspring subjects in the analysis, and on chromosomes 2 (LOD=2.1 at 242 cM) and 10(LOD=1.4 at 86 cM), 17 (LOD=1.4 at 96 cM) and 20 (LOD=1.4 at 80 cM) using both original cohort and offspring. These results suggest that there may be influential genetic regions on these chromosomes. While no linkage with genome-wide significance was detected, further research to confirm our findings is warranted.
Yang
Qiong
Q
Department of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA. qyang@bu.edu
Tofler
Geoffrey H
GH
Cupples
L Adrienne
LA
Larson
Martin G
MG
Feng
DaLi
D
Lindpaintner
Klaus
K
Levy
Daniel
D
D'Agostino
Ralph B
RB
O'Donnell
Christopher J
CJ
D000328:Adult; D001161:Arteriosclerosis / Q000453:epidemiology / Q000235:genetics; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D015331:Cohort Studies; D003327:Coronary Disease / Q000453:epidemiology / Q000235:genetics; D003920:Diabetes Mellitus / Q000453:epidemiology; D005192:Family Health; D005260:Female; D005340:Fibrinogen / Q000032:analysis* / Q000235:genetics; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000453:epidemiology; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology; D012150:Polymorphism, Restriction Fragment Length; D012307:Risk Factors
D005340:Fibrinogen