Using variance component methods implemented in the SOLAR software program, we modeled the observed phenotypic covari- ances between two individuals within the pedigree as having an expected value given by the product of their coefficient of relationship, the heritability, and the phenotypic variance of the trait. Based on this simple model, the likelihood of the pedigree data was calculated under the assumption of multivariate normality. Parameter estimation was performed by finding those values of the parameters that yielded the maximum likelihood. For dichotomous traits, SOLAR assumes an underlying liability that is continuously distributed based on the threshold model. All p-values were 2-tailed and confidence intervals set at 95%. Data were analyzed using Stata. The initial set of 166 index cases was designed to produce a population estimate of the prevalence of persistent S. aureus colonization in the population as well as to generate a sample of siblings for calculation of the prevalence rate ratio. We estimated that our final sample of 232 siblings provided 80% power to detect a prevalence rate ratio of 2.25, assuming an overall prevalence rate of 20% for persistent colonization among all siblings. In this familial aggregation study, we found that the trait of Lomeguatrib persistent S. aureus colonization does not strongly aggregate in Amish family members within different households and that heritability was low. This suggests that environmental factors or acquired host factors are more important than host genetic factors in determining persistent S. aureus colonization in this community. Colonization status is clearly influenced by multiple factors. Host factors such as age, sex, ethnicity, socioeconomic status, antibiotic use, and underlying diseases such as upper Levobetaxolol hydrochloride respiratory inflammation affect colonization. Children have higher rates of S. aureus colonization than adults perhaps due to a developing immune system. Men have a higher risk of S. aureus colonization than women. There are different carrier rates in different ethnic groups. Environmental factors such as exposure to a heavily colonized individual in the household or hospital affect colonization. Household transmission studies, which have focused mainly on MRSA, have shown that transmission from MRSA colonized patients or healthcare workers occurs in 15%–29% of household contacts. Familial aggregation was detected in a very large community-based prevalence study in the 1960’s. There was a two-fold increase in colonization if a family member was colonized ; however, colonization was defined using a single culture and family members lived in the same household. Despite this, the family pairs carried similar strains less than half the time, suggesting a genetic predisposition as opposed to common household exposure. Two twin studies have failed to find a genetic component to S. aureus carriage; these may have been underpowered and were done in pediatric populations who have different colonization patterns than adults. In our study, we controlled for household and sex by requiring sibling pairs to live in different households and to be matched on sex. We also defined S. aureus colonization using two cultures to distinguish between persistent and transient colonization. Other factors associated with S. aureus nasal carriage were restricted via eligibility criteria. Thus we were able to control for many, though not all, of the factors known to be associated with S. aureus colonization. In this setting, we did not detect strong evidence for familial aggregation or heritability.