title: African ancestry and genetic risk for uterine leiomyomata.
abstract: Rates of uterine leiomyomata (UL) are 2-3 times higher in African Americans than in European Americans. It is unclear whether inherited factors explain the ethnic disparity. To investigate the presence of risk alleles for UL that are highly differentiated in frequency between African Americans and European Americans, the authors conducted an admixture-based genome-wide scan of 2,453 UL cases confirmed by ultrasound or surgery in the Black Women's Health Study (1997-2009), a national prospective cohort study. Controls (n = 2,102) were women who did not report a UL diagnosis through 2009. Mean percentage of European ancestry was significantly lower among cases (20.00%) than among controls (21.63%; age-adjusted mean difference = -1.76%, 95% confidence interval: -2.40, -1.12; P < 0.0001), and the association was stronger in younger cases. Admixture analyses showed suggestive evidence of association at chromosomes 2, 4, and 10. The authors also genotyped a dense set of tag single nucleotide polymorphisms at different loci associated with UL in Japanese women but failed to replicate the associations. This suggests that genetic variation for UL differs in populations with and without African ancestry. The admixture findings further indicate that no single highly differentiated locus is responsible for the ethnic disparity in UL, raising the possibility that multiple variants jointly contribute to the higher incidence of UL in African Americans.
authors.affiliation: Slone Epidemiology Center at Boston University, 1010 Commonwealth Avenue, 4th Floor, Boston, MA 02215, USA. lwise@bu.edu
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Wise
authors.forename: Edward A
authors.initials: EA
authors.lastname: Ruiz-Narvaez
authors.forename: Julie R
authors.initials: JR
authors.lastname: Palmer
authors.forename: Yvette C
authors.initials: YC
authors.lastname: Cozier
authors.forename: Arti
authors.initials: A
authors.lastname: Tandon
authors.forename: Nick
authors.initials: N
authors.lastname: Patterson
authors.forename: Rose G
authors.initials: RG
authors.lastname: Radin
authors.forename: Lynn
authors.initials: L
authors.lastname: Rosenberg
authors.forename: David
authors.initials: D
authors.lastname: Reich
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D040741:Genetic Load; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D054624:Health Status Disparities; D006801:Humans; D007564:Japan / Q000453:epidemiology; D007889:Leiomyoma / Q000208:ethnology* / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017697:Premenopause; D011446:Prospective Studies; D012306:Risk; D014481:United States / Q000453:epidemiology; D014594:Uterine Neoplasms / Q000208:ethnology* / Q000235:genetics*; D044465:White People / Q000235:genetics