Uterine leiomyoma (UL) are benign neoplasms arising from the smooth muscle cells of the uterus. One of the established risk factors for UL is African American ethnicity. Studies have consistently shown that African Americans have higher risk compared with non-Hispanic Whites. However, there is still no adequate explanation for the higher risk among African Americans. Therefore, Dr. Brahim Aissani, research assistant professor in the department of epidemiology, and Dr. Kui Zhang, associate professor in the department of biostatistics, section on statistical genetics, at the University of Alabama at Birmingham — in collaboration with Dr. Howard W. Wiener, statistician in UAB’s department of epidemiology — investigated the genetic contribution to this population disparity in risk, conducting an admixture scan in 525 eligible African American women participants to the National Institute of Environmental Health Sciences uterine fibroid study (NIEHS-UFS).
The idea behind admixture mapping is simple: Genetic risk factors for diseases will be more frequent in chromosomal regions derived from the ancestral population with the higher disease rate. For recently admixed populations, such as African Americans, admixture-generated linkage disequilibrium extends many millions of base pairs; therefore, only a few thousands of ancestry informative markers that differ in frequency between the parental populations are sufficient to carry out admixture mapping studies. Another advantage of this method is that it can accommodate a case-only design, which keeps the rate of false positives low.
In models with no stratification, the investigators found multiple genomic regions showing significant and suggestive evidence of association, with chromosomal band 2q32.2 at rs256552 showing the highest score (Z-score=7.86, Bonferroni adjusted P-value=5.5 × 10−12) consistent with the suggestive evidence reported for this genomic region in the Black Women’s Health Study. However, in models stratified by the body mass index (BMI) covariate, chromosome 1q42.2 was the sole genomic region that consistently showed suggestive associations across the BMI categories tested (−6.81≤ Z-scores ≤−3.96, Bonferroni adjusted 1.4 x 10-8 ≤ P-values ≤ 0.11). In age-stratified models, a significant association was observed in the older category (age >40) reaching a Z-score of 6.44 (Bonferroni-adjusted P-value=1.64 × 10−7) at rs256552. The mean percentage of European ancestry among cases was lower than that among controls in the NIEHS-UFS study. However, the UAB study did not show a statistically significant association between mean percentage of European ancestry and UL, most likely because of insufficient statistical power in the case (n=393) and control (n=132) study.
“Admixture Mapping of Genetic Variants for Uterine Fibroids” was published in June in the Journal of Human Genetics.
Journal article: http://www.nature.com/jhg/journal/vaop/ncurrent/full/jhg201560a.html