Common genetic variation and novel loci associated with volumetric mammographic density.
Common genetic variation and novel loci associated with volumetric mammographic density.
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DOI：
10.1186/s13058-018-0954-6
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发表时间：
2018-04-17
期刊：
影响因子：
--
通讯作者：
Czene K
中科院分区：
文献类型：
--
作者：
Brand JS;Humphreys K;Li J;Karlsson R;Hall P;Czene K
乳房X线密度（MD）是乳腺癌的一种强且可遗传的中间表型，但其大部分遗传变异仍无法解释。我们在瑞典乳房 X 光检查筛查队列 (n = 9498) 中进行了体积 MD 的遗传关联研究，以确定新的 MD 基因座。使用调整年龄、体重指数、绝经状态和六个主要成分的线性回归来估计与体积MD表型（致密体积百分比、绝对致密体积和绝对非致密体积）的关联。我们还估计了 4948 名队列参与者中单核苷酸多态性（基于 SNP 的遗传力 [h2SNP]）的附加贡献所解释的 MD 方差的比例。总共，鉴定了三个新的 MD 位点（P < 5 × 10− 8）：一个用于百分比致密体积（HABP2），两个用于绝对致密体积（INHBB，LINC01483）。 INHBB 是 ER 阴性乳腺癌的既定基因座，HABP2 和 LINC01483 代表假定的新乳腺癌易感性基因座，因为在包括 122,977 例乳腺癌病例和 105,974 名对照受试者的可用荟萃分析数据中，这两个基因座均与乳腺癌相关（P < 0.05）。 h2SNP (SE) 估计的密度百分比、绝对密度和非密度体积分别为 0.29 (0.07)、0.31 (0.07) 和 0.25 (0.07)。 h2SNP 与同一队列中先前观察到的狭义 h2 估计值的对应比率分别为 0.46、0.72 和 0.41。这些发现为MD的遗传基础以及将MD与乳腺癌风险联系起来的生物学机制提供了新的见解。除了确定三个新位点外，我们还证明至少 25% 的 MD 方差可以通过常见的遗传变异来解释，其中 h2SNP/h2 比率在致密和非致密 MD 成分之间变化。本文的在线版本 (10.1186/s13058-018-0954-6) 包含补充材料，可供授权用户使用。
Mammographic density (MD) is a strong and heritable intermediate phenotype of breast cancer, but much of its genetic variation remains unexplained. We conducted a genetic association study of volumetric MD in a Swedish mammography screening cohort (n = 9498) to identify novel MD loci. Associations with volumetric MD phenotypes (percent dense volume, absolute dense volume, and absolute nondense volume) were estimated using linear regression adjusting for age, body mass index, menopausal status, and six principal components. We also estimated the proportion of MD variance explained by additive contributions from single-nucleotide polymorphisms (SNP-based heritability [h2SNP]) in 4948 participants of the cohort. In total, three novel MD loci were identified (at P < 5 × 10− 8): one for percent dense volume (HABP2) and two for the absolute dense volume (INHBB, LINC01483). INHBB is an established locus for ER-negative breast cancer, and HABP2 and LINC01483 represent putative new breast cancer susceptibility loci, because both loci were associated with breast cancer in available meta-analysis data including 122,977 breast cancer cases and 105,974 control subjects (P < 0.05). h2SNP (SE) estimates for percent dense, absolute dense, and nondense volume were 0.29 (0.07), 0.31 (0.07), and 0.25 (0.07), respectively. Corresponding ratios of h2SNP to previously observed narrow-sense h2 estimates in the same cohort were 0.46, 0.72, and 0.41, respectively. These findings provide new insights into the genetic basis of MD and biological mechanisms linking MD to breast cancer risk. Apart from identifying three novel loci, we demonstrate that at least 25% of the MD variance is explained by common genetic variation with h2SNP/h2 ratios varying between dense and nondense MD components. The online version of this article (10.1186/s13058-018-0954-6) contains supplementary material, which is available to authorized users.
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来自1,092个人基因组的遗传变异的综合图。
影响因子：
64.8
作者：
通讯作者：
--
乳房 X 光检查乳腺密度——与已确定的乳腺癌危险因素遗传相关的证据。
DOI：
10.1158/1055-9965.epi-08-0480
发表时间：
2008-12
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
--
作者：
Douglas JA;Roy-Gagnon MH;Zhou C;Mitchell BD;Shuldiner AR;Chan HP;Helvie MA
通讯作者：
Helvie MA
影响因子：
30.8
作者：
Marchini, Jonathan;Howie, Bryan;Donnelly, Peter
通讯作者：
Donnelly, Peter
影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ
影响因子：
7
作者：
Boyle AP;Hong EL;Hariharan M;Cheng Y;Schaub MA;Kasowski M;Karczewski KJ;Park J;Hitz BC;Weng S;Cherry JM;Snyder M
通讯作者：
Snyder M