Admixture mapping of uterine fibroid size and number in African American women

Michael J. Bray; Todd L. Edwards; Melissa F. Wellons; Sarah H. Jones; Katherine E. Hartmann; Digna R. Velez Edwards

doi:10.1016/j.fertnstert.2017.09.018

Admixture mapping of uterine fibroid size and number in African American women

Michael J. Bray, Todd L. Edwards, Melissa F. Wellons, Sarah H. Jones, Katherine E. Hartmann, Digna R. Velez Edwards

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

Abstract

Objective To evaluate the relationship between genetic ancestry and uterine fibroid characteristics. Design Cross-sectional study. Setting Not applicable. Patient(s) A total of 609 African American participants with image- or surgery-confirmed fibroids in a biorepository at Vanderbilt University electronic health record biorepository and the Coronary Artery Risk Development in Young Adults studies were included. Intervention(s) None. Main Outcome Measure(s) Outcome measures include fibroid number (single vs. multiple), volume of largest fibroid, and largest fibroid dimension of all fibroid measurements. Result(s) Global ancestry meta-analyses revealed a significant inverse association between percentage of European ancestry and risk of multiple fibroids (odds ratio: 0.78; 95% confidence interval 0.66, 0.93; P=6.05 × 10⁻³). Local ancestry meta-analyses revealed five suggestive (P<4.80 × 10⁻³) admixture mapping peaks in 2q14.3-2q21.1, 3p14.2-3p14.1, 7q32.2-7q33, 10q21.1, 14q24.2-14q24.3, for number of fibroids and one suggestive admixture mapping peak (P<1.97 × 10⁻³) in 10q24.1-10q24.32 for volume of largest fibroid. Single variant association meta-analyses of the strongest associated region from admixture mapping of fibroid number (10q21.1) revealed a strong association at single nucleotide polymorphism variant rs12219990 (odds ratio: 0.41; 95% confidence interval 0.28, 0.60; P=3.82 × 10⁻⁶) that was significant after correction for multiple testing. Conclusion(s) Increasing African ancestry is associated with multiple fibroids but not with fibroid size. Local ancestry analyses identified several novel genomic regions not previously associated with fibroid number and increasing volume. Future studies are needed to explore the genetic impact that ancestry plays into the development of fibroid characteristics.

Original language	English
Pages (from-to)	1034-1042.e26
Journal	Fertility and Sterility
Volume	108
Issue number	6
DOIs	https://doi.org/10.1016/j.fertnstert.2017.09.018
State	Published - Dec 2017

Bibliographical note

Publisher Copyright:
© 2017 American Society for Reproductive Medicine

Funding

Supported by CTSA award No. UL1TR000445 from the National Center for Advancing Translational Sciences. Its contents are solely the responsibility of the authors and do not necessarily represent official views of the National Center for Advancing Translational Sciences or the National Institutes of Health. Funded by the National Institutes of Health (NIH) grants (R01HD074711 and R03HD078567) to Digna R. Velez Edwards and by the Human Genetic Training Grant (5T32GM080178) and the VICTR Training Grant (6TL1TR000447) to Michael J. Bray. The Coronary Artery Risk Development in Young Adults Study (CARDIA) is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with the University of Alabama at Birmingham (HHSN268201300025C & HHSN268201300026C), Northwestern University (HHSN268201300027C), University of Minnesota (HHSN268201300028C), Kaiser Foundation Research Institute (HHSN268201300029C), and Johns Hopkins University School of Medicine (HHSN268200900041C). CARDIA is also partially supported by the Intramural Research Program of the National Institute on Aging (NIA) and an intra-agency agreement between NIA and NHLBI (AG0005). This manuscript has been reviewed by CARDIA for scientific content. The CARDIA Women's Study was supported by the NHLBI (R01-HL-065611). Genotyping was funded as part of the NHLBI Candidate-gene Association Resource (N01-HC-65226).

Funders	Funder number
National Institutes of Health (NIH)	5T32GM080178, 6TL1TR000447, R03HD078567, R01HD074711
National Institute on Aging	AG0005, R01-HL-065611
National Heart, Lung, and Blood Institute (NHLBI)
National Center for Advancing Translational Sciences (NCATS)	UL1TR000445
Northwestern Polytechnical University	HHSN268201300027C
Kaiser Foundation Research Institute	HHSN268201300029C
Minnesota State University-Mankato	HHSN268201300028C
University of Alabama, Birmingham	HHSN268201300026C, HHSN268201300025C
Johns Hopkins University School of Medicine	HHSN268200900041C

Keywords

Fibroids
admixture mapping
global ancestry
leiomyomata
local ancestry

ASJC Scopus subject areas

Reproductive Medicine
Obstetrics and Gynecology

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10.1016/j.fertnstert.2017.09.018

Cite this

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title = "Admixture mapping of uterine fibroid size and number in African American women",

abstract = "Objective To evaluate the relationship between genetic ancestry and uterine fibroid characteristics. Design Cross-sectional study. Setting Not applicable. Patient(s) A total of 609 African American participants with image- or surgery-confirmed fibroids in a biorepository at Vanderbilt University electronic health record biorepository and the Coronary Artery Risk Development in Young Adults studies were included. Intervention(s) None. Main Outcome Measure(s) Outcome measures include fibroid number (single vs. multiple), volume of largest fibroid, and largest fibroid dimension of all fibroid measurements. Result(s) Global ancestry meta-analyses revealed a significant inverse association between percentage of European ancestry and risk of multiple fibroids (odds ratio: 0.78; 95\% confidence interval 0.66, 0.93; P=6.05 × 10−3). Local ancestry meta-analyses revealed five suggestive (P<4.80 × 10−3) admixture mapping peaks in 2q14.3-2q21.1, 3p14.2-3p14.1, 7q32.2-7q33, 10q21.1, 14q24.2-14q24.3, for number of fibroids and one suggestive admixture mapping peak (P<1.97 × 10−3) in 10q24.1-10q24.32 for volume of largest fibroid. Single variant association meta-analyses of the strongest associated region from admixture mapping of fibroid number (10q21.1) revealed a strong association at single nucleotide polymorphism variant rs12219990 (odds ratio: 0.41; 95\% confidence interval 0.28, 0.60; P=3.82 × 10−6) that was significant after correction for multiple testing. Conclusion(s) Increasing African ancestry is associated with multiple fibroids but not with fibroid size. Local ancestry analyses identified several novel genomic regions not previously associated with fibroid number and increasing volume. Future studies are needed to explore the genetic impact that ancestry plays into the development of fibroid characteristics.",

keywords = "Fibroids, admixture mapping, global ancestry, leiomyomata, local ancestry",

author = "Bray, \{Michael J.\} and Edwards, \{Todd L.\} and Wellons, \{Melissa F.\} and Jones, \{Sarah H.\} and Hartmann, \{Katherine E.\} and \{Velez Edwards\}, \{Digna R.\}",

note = "Publisher Copyright: {\textcopyright} 2017 American Society for Reproductive Medicine",

year = "2017",

month = dec,

doi = "10.1016/j.fertnstert.2017.09.018",

language = "English",

volume = "108",

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number = "6",

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T1 - Admixture mapping of uterine fibroid size and number in African American women

AU - Bray, Michael J.

AU - Edwards, Todd L.

AU - Wellons, Melissa F.

AU - Jones, Sarah H.

AU - Hartmann, Katherine E.

AU - Velez Edwards, Digna R.

PY - 2017/12

Y1 - 2017/12

N2 - Objective To evaluate the relationship between genetic ancestry and uterine fibroid characteristics. Design Cross-sectional study. Setting Not applicable. Patient(s) A total of 609 African American participants with image- or surgery-confirmed fibroids in a biorepository at Vanderbilt University electronic health record biorepository and the Coronary Artery Risk Development in Young Adults studies were included. Intervention(s) None. Main Outcome Measure(s) Outcome measures include fibroid number (single vs. multiple), volume of largest fibroid, and largest fibroid dimension of all fibroid measurements. Result(s) Global ancestry meta-analyses revealed a significant inverse association between percentage of European ancestry and risk of multiple fibroids (odds ratio: 0.78; 95% confidence interval 0.66, 0.93; P=6.05 × 10−3). Local ancestry meta-analyses revealed five suggestive (P<4.80 × 10−3) admixture mapping peaks in 2q14.3-2q21.1, 3p14.2-3p14.1, 7q32.2-7q33, 10q21.1, 14q24.2-14q24.3, for number of fibroids and one suggestive admixture mapping peak (P<1.97 × 10−3) in 10q24.1-10q24.32 for volume of largest fibroid. Single variant association meta-analyses of the strongest associated region from admixture mapping of fibroid number (10q21.1) revealed a strong association at single nucleotide polymorphism variant rs12219990 (odds ratio: 0.41; 95% confidence interval 0.28, 0.60; P=3.82 × 10−6) that was significant after correction for multiple testing. Conclusion(s) Increasing African ancestry is associated with multiple fibroids but not with fibroid size. Local ancestry analyses identified several novel genomic regions not previously associated with fibroid number and increasing volume. Future studies are needed to explore the genetic impact that ancestry plays into the development of fibroid characteristics.

AB - Objective To evaluate the relationship between genetic ancestry and uterine fibroid characteristics. Design Cross-sectional study. Setting Not applicable. Patient(s) A total of 609 African American participants with image- or surgery-confirmed fibroids in a biorepository at Vanderbilt University electronic health record biorepository and the Coronary Artery Risk Development in Young Adults studies were included. Intervention(s) None. Main Outcome Measure(s) Outcome measures include fibroid number (single vs. multiple), volume of largest fibroid, and largest fibroid dimension of all fibroid measurements. Result(s) Global ancestry meta-analyses revealed a significant inverse association between percentage of European ancestry and risk of multiple fibroids (odds ratio: 0.78; 95% confidence interval 0.66, 0.93; P=6.05 × 10−3). Local ancestry meta-analyses revealed five suggestive (P<4.80 × 10−3) admixture mapping peaks in 2q14.3-2q21.1, 3p14.2-3p14.1, 7q32.2-7q33, 10q21.1, 14q24.2-14q24.3, for number of fibroids and one suggestive admixture mapping peak (P<1.97 × 10−3) in 10q24.1-10q24.32 for volume of largest fibroid. Single variant association meta-analyses of the strongest associated region from admixture mapping of fibroid number (10q21.1) revealed a strong association at single nucleotide polymorphism variant rs12219990 (odds ratio: 0.41; 95% confidence interval 0.28, 0.60; P=3.82 × 10−6) that was significant after correction for multiple testing. Conclusion(s) Increasing African ancestry is associated with multiple fibroids but not with fibroid size. Local ancestry analyses identified several novel genomic regions not previously associated with fibroid number and increasing volume. Future studies are needed to explore the genetic impact that ancestry plays into the development of fibroid characteristics.

KW - Fibroids

KW - admixture mapping

KW - global ancestry

KW - leiomyomata

KW - local ancestry

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Admixture mapping of uterine fibroid size and number in African American women

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

Access to Document

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