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NHLBI FHS (Family Heart Study)

(Michael Province, PI) – The DSG serves as the Coordinating Center for this multicenter genetic epidemiological family study of heart disease, begun in 1992.
FHSFHS-Classic (visit 1):  (Higgins et al., 1996) Extensive family and medical history data were collected on 4,000 probands (2,000 high risk and 2,000 random) and their families from 4 geographically dispersed field centers to determine the genetic risk of heart disease.  Of these families 1,200 (600 high risk and 600 random for a total ) were invited for comprehensive clinical evaluation of all major coronary disease risk factor domains, including lipids, blood pressure, obesity, lifestyle, diet, exercise, psychosocial, concurrent medications, biochemisties, pulmonary function, ECG, and carotid ultrasounds. Genotyping for candidate genes and Genome-Wide Linkage Scans (GWLS) to localize genes predisposing to heart disease and its risk factors were also performed.  
FHS SCANFHS-SCAN (visit 2): The second visit of the FHS constituted the FHS SCAN Study (Family Heart Study - Subclinical Coronary Atherosclerosis Network).  The 3,000 subjects from the largest FHS pedigrees were invited back for a second clinical exam, in which the major heart disease risk factors were re-assessed (including metabolic, behavioral, and environmental data) along with additional measures of subclinical atherosclerosis (coronary and aortic artery calcium volume) and inflammatory response.  2,767 individuals participated (including some new family members not previously examined).  In addition, a 5th field center was added and 622 African American individuals previously examined and comparably genotyped by the HyperGEN network of the Family Blood Pressure Program were enrolled at a new study center to address the study questions in this minority population.
The FHS has identified major linkage peaks for genomic regions predisposing to heart disease pathway phenotypes, which has resulted in three R01s to positionally clone QTLs for heart disease risk factors (see below).  


Major QTLs identified in FHS


Domain

Phenotype

LOD

Location

Reference

Follow-up Project

Lipids

LDL

3.7

11 (56 cM)

Coon et al., 2002

 

 

HDL

4.8

15 (70 cM)

Feitosa et al., 2007

 

 

 

3.7

5 (40 cM)

Peacock et al., 2001

 

 

Triglycerides

2.3

15 (70 cM)

Arnett et al., 2004

 

 

Triglyceride & HDL (bivar)

3.0

15 (70 cM)

 

 

Metabolic Syndrome

Principal Component Factor (BMI, WHR, SUBSCAP, TG, HDL, HMAI, PAI-1, URIC)

3.3

2 (240cM)

Tang et al., 2003

DK068320

Obesity

BMI

4.9
3.2

7 (137 cM)
13 (13q14)

Feitosa et al., 2002

HL068891
DK068336

Blood Pressure

Systolic BP
Diastolic BP

3.3
2.8

6 (89 cM)
1 (192 cM)

Hunt et al., 2002

 

Pulmonary Function

FEV1/FVC

3.5

4 (28 cM)

Wilk et al., 2003

 

Inflammation

CRP & BMI (bivar, women)

3.9

12 (138 cM)

Wu et al.2007 (in prep)

 

Atherosclerosis

Carotid Artery Plaque

2.4

2 (85 cM)

Pankow et al., 2004

 

 

Coronary Artery Calcification (CAC) x Smoking exposure

3.1
3.3
4.0
3.1

4 (122 cM)
6 (99 cM)
11 (19 cM)
13 (77 cM)

North et al., 2007