Lauren A Wise1, Julie R Palmer2, Lynn Rosenberg2, Stephen A Haddad2, Edward A Ruiz-Narváez2. 1. Slone Epidemiology Center at Boston University, Boston, Massachusetts; Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts. Electronic address: lwise@bu.edu. 2. Slone Epidemiology Center at Boston University, Boston, Massachusetts.
Abstract
OBJECTIVE: To replicate results from a previous genome-wide association study of European ancestry women, in which a positive association was found between uterine leiomyomata (UL) and rs4247357, a single-nucleotide polymorphism located near the fatty acid synthase (FASN) gene. DESIGN: Prospective cohort study. SETTING: Not applicable. PATIENT(S): African-American women aged 23-50 years, who were premenopausal and had an intact uterus in 1997. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): We genotyped rs4247357 among 2,301 incident UL cases and 3,005 controls from the Black Women's Health Study (1997-2011). Odds ratios (ORs) and 95% confidence intervals (CI) were estimated using logistic regression with control for age, geographic region of residence, and percent European ancestry using a panel of validated ancestry informative markers. RESULT(S): Overall, rs4247357 was not associated with UL risk. Relative to the CC genotype, ORs were 1.04 (95% CI 0.92-1.19) for the AC genotype and 1.09 (95% CI 0.93-1.29) for the AA genotype. A positive association was found, however, among those with higher European ancestry (≥40%). Relative to the CC genotype, ORs were 2.03 (95% CI 1.12-3.69) for the AC genotype and 2.44 (95% CI 1.20-4.96) for the AA genotype. Dietary fat intake also appeared to modify the FASN-UL association. CONCLUSION(S): Although there was little overall association between rs4247357 and UL risk, a positive association was observed among women with ≥40% European ancestry. Direct sequencing of this genomic region might be warranted to determine whether rs4247357, or some other variant, is causally related to UL.
OBJECTIVE: To replicate results from a previous genome-wide association study of European ancestry women, in which a positive association was found between uterine leiomyomata (UL) and rs4247357, a single-nucleotide polymorphism located near the fatty acid synthase (FASN) gene. DESIGN: Prospective cohort study. SETTING: Not applicable. PATIENT(S): African-American women aged 23-50 years, who were premenopausal and had an intact uterus in 1997. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): We genotyped rs4247357 among 2,301 incident UL cases and 3,005 controls from the Black Women's Health Study (1997-2011). Odds ratios (ORs) and 95% confidence intervals (CI) were estimated using logistic regression with control for age, geographic region of residence, and percent European ancestry using a panel of validated ancestry informative markers. RESULT(S): Overall, rs4247357 was not associated with UL risk. Relative to the CC genotype, ORs were 1.04 (95% CI 0.92-1.19) for the AC genotype and 1.09 (95% CI 0.93-1.29) for the AA genotype. A positive association was found, however, among those with higher European ancestry (≥40%). Relative to the CC genotype, ORs were 2.03 (95% CI 1.12-3.69) for the AC genotype and 2.44 (95% CI 1.20-4.96) for the AA genotype. Dietary fat intake also appeared to modify the FASN-UL association. CONCLUSION(S): Although there was little overall association between rs4247357 and UL risk, a positive association was observed among women with ≥40% European ancestry. Direct sequencing of this genomic region might be warranted to determine whether rs4247357, or some other variant, is causally related to UL.
Authors: Edward A Ruiz-Narváez; Lynn Rosenberg; Lauren A Wise; David Reich; Julie R Palmer Journal: Am J Epidemiol Date: 2011-01-24 Impact factor: 4.897
Authors: Liran I Shlush; Sivan Bercovici; Walter G Wasser; Guennady Yudkovsky; Alan Templeton; Dan Geiger; Karl Skorecki Journal: BMC Med Genomics Date: 2010-10-18 Impact factor: 3.063
Authors: Stacey L Eggert; Karen L Huyck; Priya Somasundaram; Raghava Kavalla; Elizabeth A Stewart; Ake T Lu; Jodie N Painter; Grant W Montgomery; Sarah E Medland; Dale R Nyholt; Susan A Treloar; Krina T Zondervan; Andrew C Heath; Pamela A F Madden; Lynda Rose; Julie E Buring; Paul M Ridker; Daniel I Chasman; Nicholas G Martin; Rita M Cantor; Cynthia C Morton Journal: Am J Hum Genet Date: 2012-10-05 Impact factor: 11.025