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Identification of novel breast cancer susceptibility loci in meta-analyses conducted among Asian and European descendants

Xiang Shu, Jirong Long, Qiuyin Cai, Sun‐Seog Kweon, Ji‐Yeob Choi, Michiaki Kubo, Sue K. Park, Manjeet K. Bolla, Joe Dennis, Qin Wang, Yaohua Yang, Jiajun Shi, Xingyi Guo, Bingshan Li, Ran Tao, Kristan J. Aronson, Kelvin Y.K. Chan, Tsun Leung Chan, Yu-Tang Gao, Mikael Hartman, Weang-Kee Ho, Hidemi Ito, Motoki Iwasaki, Hiroji Iwata, Esther M. John, Yoshio Kasuga, US Khoo, Mi Kyung Kim, Sun‐Young Kong, Allison W. Kurian, Ava Kwong, Eun Sook Lee, Jingmei Li, Artitaya Lophatananon, Siew‐Kee Low, Shivaani Mariapun, Koichi Matsuda, Keitaro Matsuo, Kenneth Muir, Dong‐Young Noh, Boyoung Park, Min Ho Park, Chen‐Yang Shen, Min‐Ho Shin, John J. Spinelli, Atsushi Takahashi, Chiu-Chen Tseng, Shoichiro Tsugane, Anna H. Wu, Yong-Bing Xiang, Taiki Yamaji, Ying Zheng, Roger L. Milne, Alison M. Dunning, Paul D.P. Pharoah, Montserrat García‐Closas, Soo‐Hwang Teo, Xiao‐Ou Shu, Daehee Kang, Douglas F. Easton, Jacques Simard, Wei Zheng

2020Nature Communications85 citationsDOIOpen Access PDF

Abstract

Abstract Known risk variants explain only a small proportion of breast cancer heritability, particularly in Asian women. To search for additional genetic susceptibility loci for breast cancer, here we perform a meta-analysis of data from genome-wide association studies (GWAS) conducted in Asians (24,206 cases and 24,775 controls) and European descendants (122,977 cases and 105,974 controls). We identified 31 potential novel loci with the lead variant showing an association with breast cancer risk at P < 5 × 10 −8 . The associations for 10 of these loci were replicated in an independent sample of 16,787 cases and 16,680 controls of Asian women ( P < 0.05). In addition, we replicated the associations for 78 of the 166 known risk variants at P < 0.05 in Asians. These findings improve our understanding of breast cancer genetics and etiology and extend previous findings from studies of European descendants to Asian women.

Topics & Concepts

Breast cancerGenome-wide association studyGenetic associationMeta-analysisHeritabilityGeneticsBiologyEtiologyCase-control studyMissing heritability problemCancerOncologyMedicineBioinformaticsInternal medicineGenetic variantsSingle-nucleotide polymorphismGeneGenotypeBRCA gene mutations in cancerGenetic Associations and EpidemiologyNutrition, Genetics, and Disease
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