A genome-wide association study of mammographic texture variation.
A genome-wide association study of mammographic texture variation.
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DOI：
10.1186/s13058-022-01570-8
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发表时间：
2022-11-07
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乳腺实质纹理特征，包括灰度变化(V)，捕捉了乳房X光照片上纹理变化的模式，并与乳腺癌风险相关，独立于乳房X光摄影密度(MD)。然而，我们对这些纹理特征的遗传基础的了解是有限的。我们对7040名欧洲血统的女性进行了一项全基因组关联研究。V评估是通过数字化胶片乳房X光片产生的。我们使用线性回归来检验调整了年龄、体重指数(BMI)、MD表型和前四个遗传主成分的单核苷酸多态(SNP)-表型关联。我们进一步计算了遗传相关性，并进行了V与MD、乳腺癌风险和其他乳腺癌风险因素的SNP集检验。我们发现了与V相关的三个全基因组显著座位：ECT2L中的rs138141444(6q24.1)，LINC01591中的rs79670367(8q24.22)，以及PGAM1P5附近的rs113174754(12q22)。6q24.1和8q24.22以前没有与MD表型或乳腺癌风险相关，而12q22是MD和乳腺癌风险的已知基因座。在已知的MD和乳腺癌风险SNPs中，我们发现了四个与处于Bonferroni校正阈值的V相关的变异，占测试SNPs的数量：PRDM6中的rs335189(5q23.2)，Ebf2中的rs13256025(8p21.2)，SSPN附近的rs11836164(12p12.1)，以及FTO中的rs17817449(16q12.2)。我们观察到V与钼靶密度(Rg = 0.79，P = 5.91 × 10−5)、百分比密度(Rg = 0.73，P = 1.00 × 10−4)和成人体重指数(Rg = − 0.36，P = 3.88 × 10−7)有显著的遗传相关。从SNP-SET测试中观察到非致密区(z = − 4.14，P = 3.42 × 10−5)、雌激素受体阳性乳腺癌(z = 3.41，P = 6.41 × 10−4)和儿童期肥胖(z = − 4.91，P = 9.05 × 10−7)的其他显著关系。这些发现为乳房X光摄影纹理变异的遗传基础及其与MD、乳腺癌风险和其他乳腺癌风险因素的关联提供了新的见解。网上版载有补充材料，可在10.1186/s13058-022-01570-8查阅。
Breast parenchymal texture features, including grayscale variation (V), capture the patterns of texture variation on a mammogram and are associated with breast cancer risk, independent of mammographic density (MD). However, our knowledge on the genetic basis of these texture features is limited. We conducted a genome-wide association study of V in 7040 European-ancestry women. V assessments were generated from digitized film mammograms. We used linear regression to test the single-nucleotide polymorphism (SNP)-phenotype associations adjusting for age, body mass index (BMI), MD phenotypes, and the top four genetic principal components. We further calculated genetic correlations and performed SNP-set tests of V with MD, breast cancer risk, and other breast cancer risk factors. We identified three genome-wide significant loci associated with V: rs138141444 (6q24.1) in ECT2L, rs79670367 (8q24.22) in LINC01591, and rs113174754 (12q22) near PGAM1P5. 6q24.1 and 8q24.22 have not previously been associated with MD phenotypes or breast cancer risk, while 12q22 is a known locus for both MD and breast cancer risk. Among known MD and breast cancer risk SNPs, we identified four variants that were associated with V at the Bonferroni-corrected thresholds accounting for the number of SNPs tested: rs335189 (5q23.2) in PRDM6, rs13256025 (8p21.2) in EBF2, rs11836164 (12p12.1) near SSPN, and rs17817449 (16q12.2) in FTO. We observed significant genetic correlations between V and mammographic dense area (rg = 0.79, P = 5.91 × 10−5), percent density (rg = 0.73, P = 1.00 × 10−4), and adult BMI (rg = − 0.36, P = 3.88 × 10−7). Additional significant relationships were observed for non-dense area (z = − 4.14, P = 3.42 × 10−5), estrogen receptor-positive breast cancer (z = 3.41, P = 6.41 × 10−4), and childhood body fatness (z = − 4.91, P = 9.05 × 10−7) from the SNP-set tests. These findings provide new insights into the genetic basis of mammographic texture variation and their associations with MD, breast cancer risk, and other breast cancer risk factors. The online version contains supplementary material available at 10.1186/s13058-022-01570-8.
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DOI：
10.1186/s13058-014-0424-8
发表时间：
2014
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Gierach GL;Li H;Loud JT;Greene MH;Chow CK;Lan L;Prindiville SA;Eng-Wong J;Soballe PW;Giambartolomei C;Mai PL;Galbo CE;Nichols K;Calzone KA;Olopade OI;Gail MH;Giger ML
通讯作者：
Giger ML
影响因子：
40.5
作者：
Loos, Ruth J. F.;Yeo, Giles S. H.
通讯作者：
Yeo, Giles S. H.
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.
影响因子：
5.2
作者：
Aguirre, Matthew;Tanigawa, Yosuke;Rivas, Manuel A.
通讯作者：
Rivas, Manuel A.
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