Identification of a novel percent mammographic density locus at 12q24

Kristen N. Stevens, Sara Lindstrom, Christopher G. Scott, Deborah Thompson, Thomas A. Sellers, Xianshu Wang, Alice Wang, Elizabeth Atkinson, David N. Rider, Jeanette E Eckel-Passow, Jajini S. Varghese, Tina Audley, Judith Brown, Jean Leyland, Robert N. Luben, Ruth M L Warren, Ruth J F Loos, Nicholas J. Wareham, Jingmei Li, Per HallJianjun Liu, Louise Eriksson, Kamila Czene, Janet E Olson, V. Shane pankratz, Zachary Fredericksen, Robert B Diasio, Adam M. Lee, John A. Heit, Mariza De Andrade, Ellen L Goode, Robert A. Vierkant, Julie M Cunningham, Sebastian M. Armasu, Richard M Weinshilboum, Brooke L. Fridley, Anthony Batzler, James N. Ingle, Norman F. Boyd, Andrew D. Paterson, Johanna Rommens, Lisa J. Martin, John L. Hopper, Melissa C. Southey, Jennifer Stone, Carmel Apicella, Peter Kraft, Susan E. Hankinson, Aditi Hazra, David J. Hunter, Douglas F. Easton, Fergus J Couch, Rulla M. Tamimi, Celine M Vachon

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Percent mammographic density adjusted for age and body mass index (BMI) is one of the strongest risk factors for breast cancer and has a heritable component that remains largely unidentified. We performed a three-stage genome-wide association study (GWAS) of percent mammographic density to identify novel genetic loci associated with this trait. In stage 1, we combined three GWASs of percent density comprised of 1241 women from studies at the Mayo Clinic and identified the top 48 loci (99 single nucleotide polymorphisms). We attempted replication of these loci in 7018 women from seven additional studies (stage 2). The meta-analysis of stage 1 and 2 data identified a novel locus, rs1265507 on 12q24, associated with percent density, adjusting for age and BMI (P = 4.43 × 10-8). We refined the 12q24 locus with 459 additional variants (stage 3) in a combined analysis of all three stages (n = 10 377) and confirmed that rs1265507 has the strongest association in the 12q24 region (P = 1.03 × 10-8). Rs1265507 is located between the genes TBX5 and TBX3, which are members of the phylogenetically conserved T-box gene family and encode transcription factors involved in developmental regulation. Understanding the mechanism underlying this association will provide insight into the genetics of breast tissue composition.

Original languageEnglish (US)
Article numberdds158
Pages (from-to)3299-3305
Number of pages7
JournalHuman Molecular Genetics
Volume21
Issue number14
DOIs
StatePublished - Jul 2012

Fingerprint

Body Mass Index
Genetic Loci
Genome-Wide Association Study
Genes
Single Nucleotide Polymorphism
Meta-Analysis
Breast
Transcription Factors
Breast Neoplasms
Breast Density

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

Cite this

Stevens, K. N., Lindstrom, S., Scott, C. G., Thompson, D., Sellers, T. A., Wang, X., ... Vachon, C. M. (2012). Identification of a novel percent mammographic density locus at 12q24. Human Molecular Genetics, 21(14), 3299-3305. [dds158]. https://doi.org/10.1093/hmg/dds158

Identification of a novel percent mammographic density locus at 12q24. / Stevens, Kristen N.; Lindstrom, Sara; Scott, Christopher G.; Thompson, Deborah; Sellers, Thomas A.; Wang, Xianshu; Wang, Alice; Atkinson, Elizabeth; Rider, David N.; Eckel-Passow, Jeanette E; Varghese, Jajini S.; Audley, Tina; Brown, Judith; Leyland, Jean; Luben, Robert N.; Warren, Ruth M L; Loos, Ruth J F; Wareham, Nicholas J.; Li, Jingmei; Hall, Per; Liu, Jianjun; Eriksson, Louise; Czene, Kamila; Olson, Janet E; Shane pankratz, V.; Fredericksen, Zachary; Diasio, Robert B; Lee, Adam M.; Heit, John A.; De Andrade, Mariza; Goode, Ellen L; Vierkant, Robert A.; Cunningham, Julie M; Armasu, Sebastian M.; Weinshilboum, Richard M; Fridley, Brooke L.; Batzler, Anthony; Ingle, James N.; Boyd, Norman F.; Paterson, Andrew D.; Rommens, Johanna; Martin, Lisa J.; Hopper, John L.; Southey, Melissa C.; Stone, Jennifer; Apicella, Carmel; Kraft, Peter; Hankinson, Susan E.; Hazra, Aditi; Hunter, David J.; Easton, Douglas F.; Couch, Fergus J; Tamimi, Rulla M.; Vachon, Celine M.

In: Human Molecular Genetics, Vol. 21, No. 14, dds158, 07.2012, p. 3299-3305.

Research output: Contribution to journalArticle

Stevens, KN, Lindstrom, S, Scott, CG, Thompson, D, Sellers, TA, Wang, X, Wang, A, Atkinson, E, Rider, DN, Eckel-Passow, JE, Varghese, JS, Audley, T, Brown, J, Leyland, J, Luben, RN, Warren, RML, Loos, RJF, Wareham, NJ, Li, J, Hall, P, Liu, J, Eriksson, L, Czene, K, Olson, JE, Shane pankratz, V, Fredericksen, Z, Diasio, RB, Lee, AM, Heit, JA, De Andrade, M, Goode, EL, Vierkant, RA, Cunningham, JM, Armasu, SM, Weinshilboum, RM, Fridley, BL, Batzler, A, Ingle, JN, Boyd, NF, Paterson, AD, Rommens, J, Martin, LJ, Hopper, JL, Southey, MC, Stone, J, Apicella, C, Kraft, P, Hankinson, SE, Hazra, A, Hunter, DJ, Easton, DF, Couch, FJ, Tamimi, RM & Vachon, CM 2012, 'Identification of a novel percent mammographic density locus at 12q24', Human Molecular Genetics, vol. 21, no. 14, dds158, pp. 3299-3305. https://doi.org/10.1093/hmg/dds158
Stevens KN, Lindstrom S, Scott CG, Thompson D, Sellers TA, Wang X et al. Identification of a novel percent mammographic density locus at 12q24. Human Molecular Genetics. 2012 Jul;21(14):3299-3305. dds158. https://doi.org/10.1093/hmg/dds158
Stevens, Kristen N. ; Lindstrom, Sara ; Scott, Christopher G. ; Thompson, Deborah ; Sellers, Thomas A. ; Wang, Xianshu ; Wang, Alice ; Atkinson, Elizabeth ; Rider, David N. ; Eckel-Passow, Jeanette E ; Varghese, Jajini S. ; Audley, Tina ; Brown, Judith ; Leyland, Jean ; Luben, Robert N. ; Warren, Ruth M L ; Loos, Ruth J F ; Wareham, Nicholas J. ; Li, Jingmei ; Hall, Per ; Liu, Jianjun ; Eriksson, Louise ; Czene, Kamila ; Olson, Janet E ; Shane pankratz, V. ; Fredericksen, Zachary ; Diasio, Robert B ; Lee, Adam M. ; Heit, John A. ; De Andrade, Mariza ; Goode, Ellen L ; Vierkant, Robert A. ; Cunningham, Julie M ; Armasu, Sebastian M. ; Weinshilboum, Richard M ; Fridley, Brooke L. ; Batzler, Anthony ; Ingle, James N. ; Boyd, Norman F. ; Paterson, Andrew D. ; Rommens, Johanna ; Martin, Lisa J. ; Hopper, John L. ; Southey, Melissa C. ; Stone, Jennifer ; Apicella, Carmel ; Kraft, Peter ; Hankinson, Susan E. ; Hazra, Aditi ; Hunter, David J. ; Easton, Douglas F. ; Couch, Fergus J ; Tamimi, Rulla M. ; Vachon, Celine M. / Identification of a novel percent mammographic density locus at 12q24. In: Human Molecular Genetics. 2012 ; Vol. 21, No. 14. pp. 3299-3305.
@article{799ddf6a554c4bd490720d7bf0ca245f,
title = "Identification of a novel percent mammographic density locus at 12q24",
abstract = "Percent mammographic density adjusted for age and body mass index (BMI) is one of the strongest risk factors for breast cancer and has a heritable component that remains largely unidentified. We performed a three-stage genome-wide association study (GWAS) of percent mammographic density to identify novel genetic loci associated with this trait. In stage 1, we combined three GWASs of percent density comprised of 1241 women from studies at the Mayo Clinic and identified the top 48 loci (99 single nucleotide polymorphisms). We attempted replication of these loci in 7018 women from seven additional studies (stage 2). The meta-analysis of stage 1 and 2 data identified a novel locus, rs1265507 on 12q24, associated with percent density, adjusting for age and BMI (P = 4.43 × 10-8). We refined the 12q24 locus with 459 additional variants (stage 3) in a combined analysis of all three stages (n = 10 377) and confirmed that rs1265507 has the strongest association in the 12q24 region (P = 1.03 × 10-8). Rs1265507 is located between the genes TBX5 and TBX3, which are members of the phylogenetically conserved T-box gene family and encode transcription factors involved in developmental regulation. Understanding the mechanism underlying this association will provide insight into the genetics of breast tissue composition.",
author = "Stevens, {Kristen N.} and Sara Lindstrom and Scott, {Christopher G.} and Deborah Thompson and Sellers, {Thomas A.} and Xianshu Wang and Alice Wang and Elizabeth Atkinson and Rider, {David N.} and Eckel-Passow, {Jeanette E} and Varghese, {Jajini S.} and Tina Audley and Judith Brown and Jean Leyland and Luben, {Robert N.} and Warren, {Ruth M L} and Loos, {Ruth J F} and Wareham, {Nicholas J.} and Jingmei Li and Per Hall and Jianjun Liu and Louise Eriksson and Kamila Czene and Olson, {Janet E} and {Shane pankratz}, V. and Zachary Fredericksen and Diasio, {Robert B} and Lee, {Adam M.} and Heit, {John A.} and {De Andrade}, Mariza and Goode, {Ellen L} and Vierkant, {Robert A.} and Cunningham, {Julie M} and Armasu, {Sebastian M.} and Weinshilboum, {Richard M} and Fridley, {Brooke L.} and Anthony Batzler and Ingle, {James N.} and Boyd, {Norman F.} and Paterson, {Andrew D.} and Johanna Rommens and Martin, {Lisa J.} and Hopper, {John L.} and Southey, {Melissa C.} and Jennifer Stone and Carmel Apicella and Peter Kraft and Hankinson, {Susan E.} and Aditi Hazra and Hunter, {David J.} and Easton, {Douglas F.} and Couch, {Fergus J} and Tamimi, {Rulla M.} and Vachon, {Celine M}",
year = "2012",
month = "7",
doi = "10.1093/hmg/dds158",
language = "English (US)",
volume = "21",
pages = "3299--3305",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "14",

}

TY - JOUR

T1 - Identification of a novel percent mammographic density locus at 12q24

AU - Stevens, Kristen N.

AU - Lindstrom, Sara

AU - Scott, Christopher G.

AU - Thompson, Deborah

AU - Sellers, Thomas A.

AU - Wang, Xianshu

AU - Wang, Alice

AU - Atkinson, Elizabeth

AU - Rider, David N.

AU - Eckel-Passow, Jeanette E

AU - Varghese, Jajini S.

AU - Audley, Tina

AU - Brown, Judith

AU - Leyland, Jean

AU - Luben, Robert N.

AU - Warren, Ruth M L

AU - Loos, Ruth J F

AU - Wareham, Nicholas J.

AU - Li, Jingmei

AU - Hall, Per

AU - Liu, Jianjun

AU - Eriksson, Louise

AU - Czene, Kamila

AU - Olson, Janet E

AU - Shane pankratz, V.

AU - Fredericksen, Zachary

AU - Diasio, Robert B

AU - Lee, Adam M.

AU - Heit, John A.

AU - De Andrade, Mariza

AU - Goode, Ellen L

AU - Vierkant, Robert A.

AU - Cunningham, Julie M

AU - Armasu, Sebastian M.

AU - Weinshilboum, Richard M

AU - Fridley, Brooke L.

AU - Batzler, Anthony

AU - Ingle, James N.

AU - Boyd, Norman F.

AU - Paterson, Andrew D.

AU - Rommens, Johanna

AU - Martin, Lisa J.

AU - Hopper, John L.

AU - Southey, Melissa C.

AU - Stone, Jennifer

AU - Apicella, Carmel

AU - Kraft, Peter

AU - Hankinson, Susan E.

AU - Hazra, Aditi

AU - Hunter, David J.

AU - Easton, Douglas F.

AU - Couch, Fergus J

AU - Tamimi, Rulla M.

AU - Vachon, Celine M

PY - 2012/7

Y1 - 2012/7

N2 - Percent mammographic density adjusted for age and body mass index (BMI) is one of the strongest risk factors for breast cancer and has a heritable component that remains largely unidentified. We performed a three-stage genome-wide association study (GWAS) of percent mammographic density to identify novel genetic loci associated with this trait. In stage 1, we combined three GWASs of percent density comprised of 1241 women from studies at the Mayo Clinic and identified the top 48 loci (99 single nucleotide polymorphisms). We attempted replication of these loci in 7018 women from seven additional studies (stage 2). The meta-analysis of stage 1 and 2 data identified a novel locus, rs1265507 on 12q24, associated with percent density, adjusting for age and BMI (P = 4.43 × 10-8). We refined the 12q24 locus with 459 additional variants (stage 3) in a combined analysis of all three stages (n = 10 377) and confirmed that rs1265507 has the strongest association in the 12q24 region (P = 1.03 × 10-8). Rs1265507 is located between the genes TBX5 and TBX3, which are members of the phylogenetically conserved T-box gene family and encode transcription factors involved in developmental regulation. Understanding the mechanism underlying this association will provide insight into the genetics of breast tissue composition.

AB - Percent mammographic density adjusted for age and body mass index (BMI) is one of the strongest risk factors for breast cancer and has a heritable component that remains largely unidentified. We performed a three-stage genome-wide association study (GWAS) of percent mammographic density to identify novel genetic loci associated with this trait. In stage 1, we combined three GWASs of percent density comprised of 1241 women from studies at the Mayo Clinic and identified the top 48 loci (99 single nucleotide polymorphisms). We attempted replication of these loci in 7018 women from seven additional studies (stage 2). The meta-analysis of stage 1 and 2 data identified a novel locus, rs1265507 on 12q24, associated with percent density, adjusting for age and BMI (P = 4.43 × 10-8). We refined the 12q24 locus with 459 additional variants (stage 3) in a combined analysis of all three stages (n = 10 377) and confirmed that rs1265507 has the strongest association in the 12q24 region (P = 1.03 × 10-8). Rs1265507 is located between the genes TBX5 and TBX3, which are members of the phylogenetically conserved T-box gene family and encode transcription factors involved in developmental regulation. Understanding the mechanism underlying this association will provide insight into the genetics of breast tissue composition.

UR - http://www.scopus.com/inward/record.url?scp=84864004783&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84864004783&partnerID=8YFLogxK

U2 - 10.1093/hmg/dds158

DO - 10.1093/hmg/dds158

M3 - Article

C2 - 22532574

AN - SCOPUS:84864004783

VL - 21

SP - 3299

EP - 3305

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 14

M1 - dds158

ER -