Identification of 31 loci for mammographic density phenotypes and their associations with breast cancer risk.
Identification of 31 loci for mammographic density phenotypes and their associations with breast cancer risk.
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DOI：
10.1038/s41467-020-18883-x
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发表时间：
2020-10-09
影响因子：
16.6
通讯作者：
Habel LA
中科院分区：
文献类型：
--
作者：
Sieh W;Rothstein JH;Klein RJ;Alexeeff SE;Sakoda LC;Jorgenson E;McBride RB;Graff RE;McGuire V;Achacoso N;Acton L;Liang RY;Lipson JA;Rubin DL;Yaffe MJ;Easton DF;Schaefer C;Risch N;Whittemore AS;Habel LA
乳腺摄影密度（MD）表型与乳腺癌风险密切相关，并且具有高度遗传性。在这项对24,192名女性的GWAS荟萃分析中，我们在P < 5 × 10−8时确定了31个MD位点，是已知的46个的三倍。在独立的荟萃分析中，17个MD位点也与乳腺癌风险相关（P < 0.05）。孟德尔随机化分析显示，密度区（DA）、非密度区（NDA）和密度百分比（PD）的遗传估计值均与乳腺癌风险显著相关（P < 0.05）。通路分析揭示了涉及DA、NDA和PD位点的不同生物学过程。这些发现为MD表型的遗传基础及其与乳腺癌风险的关联提供了额外的见解。乳腺摄影密度是乳腺癌风险的最强预测因子之一。在这里，作者对接受全视野数字乳腺X射线摄影筛查的女性进行了全基因组关联研究荟萃分析，并确定了31个先前未报告的与乳腺X射线摄影密度表型相关的基因座。
Mammographic density (MD) phenotypes are strongly associated with breast cancer risk and highly heritable. In this GWAS meta-analysis of 24,192 women, we identify 31 MD loci at P < 5 × 10−8, tripling the number known to 46. Seventeen identified MD loci also are associated with breast cancer risk in an independent meta-analysis (P < 0.05). Mendelian randomization analyses show that genetic estimates of dense area (DA), nondense area (NDA), and percent density (PD) are all significantly associated with breast cancer risk (P < 0.05). Pathway analyses reveal distinct biological processes involving DA, NDA and PD loci. These findings provide additional insights into the genetic basis of MD phenotypes and their associations with breast cancer risk. Mammographic density represents one the strongest predictors of breast cancer risk. Here the authors perform genome-wide association study meta-analysis of women screened with full-field digital mammography and identify 31 previously unreported loci associated with mammographic density phenotypes.
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影响因子：
3.7
作者：
Hayes JE;Trynka G;Vijai J;Offit K;Raychaudhuri S;Klein RJ
通讯作者：
Klein RJ
影响因子：
2.5
作者：
Hovey, Russell C.;Aimo, Lucila
通讯作者：
Aimo, Lucila
DOI：
10.1186/s13058-016-0715-3
发表时间：
2016-05-21
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Habel LA;Lipson JA;Achacoso N;Rothstein JH;Yaffe MJ;Liang RY;Acton L;McGuire V;Whittemore AS;Rubin DL;Sieh W
通讯作者：
Sieh W
影响因子：
2.1
作者：
Bowden J;Davey Smith G;Haycock PC;Burgess S
通讯作者：
Burgess S
影响因子：
30.8
作者：
Bulik-Sullivan, Brendan K.;Loh, Po-Ru;Finucane, Hilary K.;Ripke, Stephan;Yang, Jian;Patterson, Nick;Daly, Mark J.;Price, Alkes L.;Neale, Benjamin M.
通讯作者：
Neale, Benjamin M.