XXXX risk in siblings with @entity3458 .

@entity1 @entity64 @entity66 @entity3458 @entity1188 @entity2395
@entity66 is a common cause of morbidity in @entity3458 (HbSS): approximately 10% of @entity1 have a clinical @entity64 before 20 years of age, and another 22% have silent @entity1188 on magnetic resonance imaging. The phenotypic variation among @entity1 with HbSS suggests a role for modifier genes and/or environmental influences. To assess the familial component of clinical @entity64 in HbSS, we estimated the prevalence of clinical @entity64 among all @entity1 and among HbSS sibling pairs at 9 pediatric centers. The sample included 3425 @entity1 with @entity3458 who were younger than 21 years, including 2353 @entity1 with HbSS. The @entity64 prevalence was 4.9% for all genotypes; 7.1% for @entity1 with HbSS; 1.1% for @entity1 with @entity2395 ; 0.6% for @entity1 with @entity2395 ; and 0% for @entity1 with HbSC. In 207 sibships, more than 1 @entity1 had HbSS. There were 42 sibships in which at least 1 sibling had a @entity64 , and in 10 of the 42, 2 siblings had a @entity64 . A permutation test indicated that the number of families in which 2 @entity1 had @entity64 was larger than the number expected if @entity64 were randomly distributed among @entity1 in sibships (P =.0012). There was no difference in @entity64 prevalence based on sex, nor was the mean age at @entity64 presentation significantly different between singletons and sibships with @entity64 . We conclude that there is a familial predisposition to @entity64 in HbSS. Attempts to identify genetic modifiers should be initiated with family-based studies.
