NHLBI Family Heart Study (FamHS)

The Family Heart Study (FamHS) was funded by the National Heart, Lung, and Blood Institute (NHLBI). It was begun in 1992 with the ascertainment of 1,200 families, half randomly sampled, and half selected because of an excess of coronary heart disease (CHD) or risk factor abnormalities as compared with age- and sex-specific population rates (Higgins et al. 1996). The families, with approximately 6,000 individuals, were sampled on the basis of information on probands from four population-based parent studies: the Framingham Heart Study, the Utah Family Tree Study, and two Atherosclerosis Risk in Communities (ARIC) centers (Minneapolis, and Forsyth County, NC). A broad range of phenotypes were assessed at a clinic examination in broad domains of CHD, atherosclerosis, cardiac and vascular function, inflammation and hemostasis, lipids and lipoproteins, blood pressure, diabetes and insulin resistance, pulmonary function, and anthropometry (FamHS Visit 1). Approximately 8 years later, study participants belonging to the largest pedigrees were invited for a second clinical exam (FamHS Visit 2). A total of 2,756 Caucasian subjects in 508 extended families were examined. A two-phase design was adopted for the genome wide association (GWA) study. In phase-1, 1007 subjects were chosen, equally distributed between the upper and lower quartile of age- and sex-adjusted values for coronary artery calcification, assessed by CT scan in Visit 2. These subjects were chosen to be largely unrelated; 34% of the subjects were from unique families, while 200 other subjects had 1 or more siblings selected into the sample, yielding a sample of 465 unrelated subjects. The remaining family members (N=1749) were genotyped in the phase-2 for replication of the top hits from the phase-1. The results presented here represent those for the analysis of the phase-1 case-control sample for variables assessed in FamHS Visit 1 (from 1992 to 1995) and for the variables assessed in FamHS Visit 2 (from 2002 to 2003). All subjects were typed on the Illumina HumMap 550 chip (Phase 1 genotype). Of these, 33 (3.3%) were excluded due to technical errors, call rates below 98%, and discrepancies between reported sex and sex-diagnostic markers. The final sample of 974 subjects have Visit 2 phenotypes, approximately 100 of these do not have Visit 1 phenotypes. There was no significant plate-to-plate variation in allele frequencies. The covariate adjustments were performed separately by sex using cubic polynomial age and clinical centers, and retaining the terms in the stepwise regression analysis that were significant at the 5% level. Extreme outliers (>4 SD from the mean) were set aside, temporarily, for the adjustments. The final phenotypes were computed for all individuals using the best mean regression models and standardizing to 0 mean and unit variance. The FamHS has contributed GWA results in many phenotype domains (antropometric and adiposity, atherosclerosis and coronary heart disease, lipid profile, diabetes and glicemic traits, metabolic syndrome etc) to meta-analyses and various consortia, including Heard-Costa et al. 2009, Köttgen et al. 2010, Teslovich et al. 2010, Nettleton et al. 2010, Lango et al. 2010, Heid et al. 2010, Speliotes et al. 2010, Dupuis et al. 2010, Kraja et al. 2011.]]>
"Body Mass Index(Weight in kg/ Height in m^2)" at Visit 1. The sample size is 856 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Body Mass Index(Weight in kg/Height in m^2)" at Visit 2. The sample size is 974 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Elbow Breadth (mm)" at Visit 1. The sample size is 851 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Fat Free Mass Lewis" at Visit 2. The sample size is 813 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Height (cm)" at Visit 1. The sample size is 856 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Height(m)" at Visit 2. The sample size is 974 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Log Transformed Subscapular/Triceps Ratio (mm)" at Visit 1. The sample size is 855 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Log Transformed Waist to Hip Ratio (cm)" at Visit 2. The sample size is 973 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Obesity World Health Organization (unaffected: BMI<30kg/m2, affected: BMI≥30kg/m2)" at Visit 1. The sample size is 856 and the covariates for this categorical trait are age, age squared, age cubed, sex, clinical centers.
]]>"Obesity World Health Organization (unaffected: BMI<30kg/m2, affected: BMI≥30kg/m2)" at Visit 2. The sample size is 974 and the covariates for this categorical trait are age, age squared, age cubed, sex, clinical centers.
]]>"Percent Body Fat Elderly" at Visit 2. The sample size is 813 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Percent Body Fat Lukaski" at Visit 2. The sample size is 809 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Percent Body Fat Native American" at Visit 2. The sample size is 812 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Subscapular+Triceps (mm)" at Visit 1. The sample size is 855 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Mean of 2 Subscapular Measurments (mm)" at Visit 1. The sample size is 855 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Subscapular/Triceps Ratio (mm)" at Visit 1. The sample size is 855 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Mean of 2 Triceps Measurements (mm)" at Visit 1. The sample size is 855 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Waist Girth (cm) Adjusted for Age, Sex, Clinical Centers ,and BMI" at Visit 1. The sample size is 855 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers, BMI.
]]>"Waist Girth (cm)" at Visit 1. The sample size is 855 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Waist Girth (cm)" at Visit 2. The sample size is 973 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Weight (lb)" at Visit 1. The sample size is 856 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Weight (lb)" at Visit 2. The sample size is 974 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Waist to Hip Ratio (cm)" at Visit 2. The sample size is 973 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Waist to Hip Ratio (cm)" at Visit 1. The sample size is 855 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"BLOM Transformed AORTA Calcium" at Visit 2. The sample size is 973 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"BLOM Transformed CAC, Coronary Calcium" at Visit 2. The sample size is 974 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Calculated Common Arterial Diameter" at Visit 1. The sample size is 821 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Internal Arterial Diameter" at Visit 1. The sample size is 794 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Log Transformed Calculated Bifurcation Far Intima-Media Wall Thickness" at Visit 1. The sample size is 742 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Log Transformed Calculated Optimal Bifurcation Arterial Diameter" at Visit 1. The sample size is 724 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Log Transformed Calculated Optimal Bifurcation Far Intima-Media Wall Thickness" at Visit 1. The sample size is 674 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Log Transformed Calculated Common Far Intima-Media Wall Thickness" at Visit 1. The sample size is 798 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Log Transformed Calculated Internal Far Intima-Media Wall Thickness" at Visit 1. The sample size is 631 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Average 2nd & 3rd Diastolic Blood Pressure mmHg" at Visit 2. The sample size is 974 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Average 2nd &3rd Diastolic Blood Pressure mmHg" at Visit 1. The sample size is 854 and the covariates are age, age squared, age cubed, sex, clinical centers.
]]>"Taking Medication for Hypertension or Systolic Blood Pressure≥140 or Diastolic Blood Pressure≥90" at Visit 1. The sample size is 897 and the covariates for this categorical trait are age, age squared, age cubed, sex, clinical centers.
]]>"Taking Medication for Hypertension or Systolic Blood Pressure≥140 or Diastolic Blood Pressure≥90" at Visit 2. The sample size is 974 and the covariates for this categorical trait are age, age squared, age cubed, sex, clinical centers.
]]>"Index of Ankle over Arm/DBP" at Visit 1. The sample size is 683 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Index of Ankle over Arm/SBP" at Visit 1. The sample size is 683 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Mean Arterial Pressure" at Visit 2. The sample size is 974 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Pulse Obliteration Pressure" at Visit 1. The sample size is 851 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Average 2nd & 3rd Systolic Blood Pressure mmHg" at Visit 2. The sample size is 974 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Average 2nd & 3rd Systolic Blood Pressure mmHg" at Visit 1. The sample size is 854 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Average 1st & 2nd Standing Diastolic Blood Pressure mmHg" at Visit 1. The sample size is 669 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Average 1st & 2nd Standing Systolic Blood Pressure mmHg" at Visit 1. The sample size is 669 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Log Transformed Heart Rate Beats per Minute" at Visit 1. The sample size is 853 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Log Transformed Left Ventricular Hypertrophy Index" at Visit 1. The sample size is 851 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"QT index" at Visit 1. The sample size is 851 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"QT interval, MSEC" at Visit 1. The sample size is 853 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Derived Coronary Heart Disease (Miocardial Infarction or Bypass Operation or Balloon Angioplasty)" at Visit 1. The sample size is 889 and the covariates for this categorical trait are age, age squared, age cubed, sex, clinical centers.
]]>"Derived Coronary Heart Disease (Miocardial Infarction or Bypass Operation or Balloon Angioplasty)" at Visit 2. The sample size is 974 and the covariates for this categorical trait are age, age squared, age cubed, sex, clinical centers.
]]>"BLOM Transformed Glucose mg/dL(1/gluc*gluc)" at Visit 2. The sample size is 960 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"BLOM Transformed Glucose mg/dL" at Visit 1. The sample size is 874 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Taking Medication for Diabetes or Glucose mg/dL ≥126" at Visit 1. The sample size is 875 and the covariates for this categorical trait are age, age squared, age cubed, sex, clinical centers.
]]>"Taking Medication for Diabetes or Glucose mg/dL ≥126" at Visit 2. The sample size is 962 and the covariates for this categorical trait are age, age squared, age cubed, sex, clinical centers.
]]>"Glucose mg/dL(1/glucose*glucose)" at Visit 1. The sample size is 874 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Log Transformed HOMA (Homeostasis Model Assessment Insulin Resistance Index)=INSULIN*GLUCOSE/22.5" at Visit 1. The sample size is 870 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Log Transformed Insulin mU/L" at Visit 1. The sample size is 870 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Meta bolic syndrome - NCEP" at Visit 1. The sample size is 897 and the covariates are age, age squared, age cubed, sex, clinical centers.
]]>"Metabolic syndrome - NCEP" at Visit 2. The sample size is 974 and the covariates are age, age squared, age cubed, sex, clinical centers.
]]>"Sum Job Strain factors-Lifestyle:Dissatisfaction,Exertion,Insecurity,Latitude,Workload" at Visit 1. The sample size is 804 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Sum Social Support Factors-Lifestyle:Instrumental,Emotional,Society,Network" at Visit 1. The sample size is 838 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Fibrinogen mg/dL" at Visit 1. The sample size is 842 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Log Transformed Creatinine mg/dL" at Visit 1. The sample size is 883 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Log Transformed C Reative Protein (mg/L)" at Visit 2. The sample size is 953 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Log Transformed Monocyte Chemoattractant Protein-1(pg/ml)" at Visit 2. The sample size is 926 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Intercellular adhesion molecule(ng/mL)" at Visit 2. The sample size is 963 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Cholesterol mg/dL" at Visit 1. The sample size is 872 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"High-Density Lipoprotein Cholesterol mg/dL" at Visit 1. The sample size is 872 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"High-Density Lipoprotein Cholesterol mg/dL" at Visit 2. The sample size is 959 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Low-Density Lipoprotein Cholesterol mg/dL" at Visit 1. The sample size is 872 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Low-Density Lipoprotein Cholesterol mg/dL" at Visit 2. The sample size is 944 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Log Transformed Cholesterol mg/dL" at Visit 1. The sample size is 872 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Log Transformed Derived Lipoprotein(a) mg/dL" at Visit 1. The sample size is 876 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Log Transformed Triglycerides mg/dL" at Visit 1. The sample size is 872 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Log Transformed Triglycerides mg/dL" at Visit 2. The sample size is 960 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Log Transformed TG/HDL" at Visit 2. The sample size is 959 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Log Transformed Cholesterol mg/dL" at Visit 2. The sample size is 960 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Albumin g/dL" at Visit 1. The sample size is 883 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Calcium mg/dL" at Visit 1. The sample size is 883 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Potassium mmol/L" at Visit 1. The sample size is 883 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Log Transformed Relative Basophil%" at Visit 1. The sample size is 710 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Log Transformed Relative Eosinophil%" at Visit 1. The sample size is 710 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Log Transformed Relative Monocyte%" at Visit 1. The sample size is 710 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Log Transformed Red Blood Cell Distribution Width%" at Visit 1. The sample size is 767 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Log Transformed White Blood Cell Count 10e9/L" at Visit 1. The sample size is 849 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Magnesium mg/dL" at Visit 1. The sample size is 883 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Sodium mmol/L" at Visit 1. The sample size is 883 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Relative Lymphocyte%" at Visit 1. The sample size is 710 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Relative Neutrophil%" at Visit 1. The sample size is 717 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Hemoglobin g/dL" at Visit 1. The sample size is 849 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Hematocrit%" at Visit 1. The sample size is 849 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Mean Red Blood Cell Hemoglobin pg" at Visit 1. The sample size is 767 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Mean Red Blood Cell Volume fl" at Visit 1. The sample size is 767 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Platelet Count 10e9/L" at Visit 1. The sample size is 849 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Red Blood Cell Count 10e12/L" at Visit 1. The sample size is 767 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Forced Expiratory Volume/1sec (FEV1)" at Visit 1. The sample size is 821 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Derived FEV1/FVC Ratio" at Visit 1. The sample size is 816 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>"Forced Vital Capacity (FVC)" at Visit 1. The sample size is 821 and the covariates are Age, Age squared, Age cubed, Sex, Clinical Centers.
]]>(1) FamHS Visit 1: There were randomly chosen families and high risk families. The high risk families were based upon the Framingham Family Risk Score, which in turn was based upon the number of family members with validated Coronary Heart Disease (CHD) Events defined as any of Myocardial Infarction, Bypass Operation, or Balloon Angioplasty. Families with two or more CHD events and risk scores of 0.5 or higher were considered to be eligible as a high risk family. Probands aged 45 or older and Family members aged 25 or older were offered clinic examinations provided that at least 50% of the eligible members, including at least two biologically related individuals returned personal medical histories. Random sample families were invited to clinic examinations using the same age and response criteria, but without regard to history of CHD. (2) FamHS Visit 2: Family members were included if they were members of Families who participated in Visit 1, above, and were at least 30 years old. Participants were Excluded from Visit 2, if they were Pregnant, or unwilling to have a CT scan, or were below age 30 years or were heavier than the maximum weight for the local CT scanner. Women who had recently been pregnant needed to be 6 or more months postpartum by the time of their clinic exam and CT scan in order to be included.]]>