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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.

SUBMITTER: Stevens KN 

PROVIDER: S-EPMC3384385 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Identification of a novel percent mammographic density locus at 12q24.

Stevens Kristen N KN   Lindstrom Sara S   Scott Christopher G CG   Thompson Deborah D   Sellers Thomas A TA   Wang Xianshu X   Wang Alice A   Atkinson Elizabeth E   Rider David N DN   Eckel-Passow Jeanette E JE   Varghese Jajini S JS   Audley Tina T   Brown Judith J   Leyland Jean J   Luben Robert N RN   Warren Ruth M L RM   Loos Ruth J F RJ   Wareham Nicholas J NJ   Li Jingmei J   Hall Per P   Liu Jianjun J   Eriksson Louise L   Czene Kamila K   Olson Janet E JE   Pankratz V Shane VS   Fredericksen Zachary Z   Diasio Robert B RB   Lee Adam M AM   Heit John A JA   DeAndrade Mariza M   Goode Ellen L EL   Vierkant Robert A RA   Cunningham Julie M JM   Armasu Sebastian M SM   Weinshilboum Richard R   Fridley Brooke L BL   Batzler Anthony A   Ingle James N JN   Boyd Norman F NF   Paterson Andrew D AD   Rommens Johanna J   Martin Lisa J LJ   Hopper John L JL   Southey Melissa C MC   Stone Jennifer J   Apicella Carmel C   Kraft Peter P   Hankinson Susan E SE   Hazra Aditi A   Hunter David J DJ   Easton Douglas F DF   Couch Fergus J FJ   Tamimi Rulla M RM   Vachon Celine M CM  

Human molecular genetics 20120424 14


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  ...[more]

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