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 L Chan; Yu-Tang Gao; Mikael Hartman; Weang Kee Ho; Hidemi Ito; Motoki Iwasaki; Hiroji Iwata; Esther M John; Yoshio Kasuga; Ui Soon 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; Chiuchen 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

doi:10.1038/s41467-020-15046-w

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 L Chan, Yu-Tang Gao, Mikael HartmanWeang Kee Ho, Hidemi Ito, Motoki Iwasaki, Hiroji Iwata, Esther M John, Yoshio Kasuga, Ui Soon 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, Chiuchen 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

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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.

Original language	English
Pages (from-to)	1217
Journal	Nature Communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-15046-w
Publication status	Published - 5 Mar 2020

Keywords

Asian Continental Ancestry Group/genetics
Breast Neoplasms/genetics
European Continental Ancestry Group/genetics
Female
Genetic Loci
Genetic Predisposition to Disease
Humans
Multifactorial Inheritance/genetics
Polymorphism, Single Nucleotide/genetics
Quantitative Trait Loci/genetics
Receptors, Estrogen/metabolism
Risk Factors

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Shu, X., Long, J., Cai, Q., Kweon, S.-S., Choi, J.-Y., Kubo, M., Park, S. K., Bolla, M. K., Dennis, J., Wang, Q., Yang, Y., Shi, J., Guo, X., Li, B., Tao, R., Aronson, K. J., Chan, K. Y. K., Chan, T. L., Gao, Y.-T., ... Zheng, W. (2020). Identification of novel breast cancer susceptibility loci in meta-analyses conducted among Asian and European descendants. Nature Communications, 11(1), 1217. https://doi.org/10.1038/s41467-020-15046-w

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

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.",

keywords = "Asian Continental Ancestry Group/genetics, Breast Neoplasms/genetics, European Continental Ancestry Group/genetics, Female, Genetic Loci, Genetic Predisposition to Disease, Humans, Multifactorial Inheritance/genetics, Polymorphism, Single Nucleotide/genetics, Quantitative Trait Loci/genetics, Receptors, Estrogen/metabolism, Risk Factors",

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

year = "2020",

month = mar,

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doi = "10.1038/s41467-020-15046-w",

language = "English",

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journal = "Nature Communications",

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Shu, X, Long, J, Cai, Q, Kweon, S-S, Choi, J-Y, Kubo, M, Park, SK, Bolla, MK, Dennis, J, Wang, Q, Yang, Y, Shi, J, Guo, X, Li, B, Tao, R, Aronson, KJ, Chan, KYK, Chan, TL, Gao, Y-T, Hartman, M, Kee Ho, W, Ito, H, Iwasaki, M, Iwata, H, John, EM, Kasuga, Y, Soon Khoo, U, Kim, M-K, Kong, S-Y, Kurian, AW, Kwong, A, Lee, E-S, Li, J, Lophatananon, A, Low, S-K, Mariapun, S, Matsuda, K, Matsuo, K, Muir, K, Noh, D-Y, Park, B, Park, M-H, Shen, C-Y, Shin, M-H, Spinelli, JJ, Takahashi, A, Tseng, C, Tsugane, S, Wu, AH, Xiang, Y-B, Yamaji, T, Zheng, Y, Milne, RL, Dunning, AM, Pharoah, PDP, García-Closas, M, Teo, S-H, Shu, X-O, Kang, D, Easton, DF, Simard, J & Zheng, W 2020, 'Identification of novel breast cancer susceptibility loci in meta-analyses conducted among Asian and European descendants', Nature Communications, vol. 11, no. 1, pp. 1217. https://doi.org/10.1038/s41467-020-15046-w

TY - JOUR

T1 - Identification of novel breast cancer susceptibility loci in meta-analyses conducted among Asian and European descendants

AU - Shu, Xiang

AU - Long, Jirong

AU - Cai, Qiuyin

AU - Kweon, Sun-Seog

AU - Choi, Ji-Yeob

AU - Kubo, Michiaki

AU - Park, Sue K

AU - Bolla, Manjeet K

AU - Dennis, Joe

AU - Wang, Qin

AU - Yang, Yaohua

AU - Shi, Jiajun

AU - Guo, Xingyi

AU - Li, Bingshan

AU - Tao, Ran

AU - Aronson, Kristan J

AU - Chan, Kelvin Y K

AU - Chan, Tsun L

AU - Gao, Yu-Tang

AU - Hartman, Mikael

AU - Kee Ho, Weang

AU - Ito, Hidemi

AU - Iwasaki, Motoki

AU - Iwata, Hiroji

AU - John, Esther M

AU - Kasuga, Yoshio

AU - Soon Khoo, Ui

AU - Kim, Mi-Kyung

AU - Kong, Sun-Young

AU - Kurian, Allison W

AU - Kwong, Ava

AU - Lee, Eun-Sook

AU - Li, Jingmei

AU - Lophatananon, Artitaya

AU - Low, Siew-Kee

AU - Mariapun, Shivaani

AU - Matsuda, Koichi

AU - Matsuo, Keitaro

AU - Muir, Kenneth

AU - Noh, Dong-Young

AU - Park, Boyoung

AU - Park, Min-Ho

AU - Shen, Chen-Yang

AU - Shin, Min-Ho

AU - Spinelli, John J

AU - Takahashi, Atsushi

AU - Tseng, Chiuchen

AU - Tsugane, Shoichiro

AU - Wu, Anna H

AU - Xiang, Yong-Bing

AU - Yamaji, Taiki

AU - Zheng, Ying

AU - Milne, Roger L

AU - Dunning, Alison M

AU - Pharoah, Paul D P

AU - García-Closas, Montserrat

AU - Teo, Soo-Hwang

AU - Shu, Xiao-Ou

AU - Kang, Daehee

AU - Easton, Douglas F

AU - Simard, Jacques

AU - Zheng, Wei

PY - 2020/3/5

Y1 - 2020/3/5

N2 - 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.

AB - 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.

KW - Asian Continental Ancestry Group/genetics

KW - Breast Neoplasms/genetics

KW - European Continental Ancestry Group/genetics

KW - Female

KW - Genetic Loci

KW - Genetic Predisposition to Disease

KW - Humans

KW - Multifactorial Inheritance/genetics

KW - Polymorphism, Single Nucleotide/genetics

KW - Quantitative Trait Loci/genetics

KW - Receptors, Estrogen/metabolism

KW - Risk Factors

U2 - 10.1038/s41467-020-15046-w

DO - 10.1038/s41467-020-15046-w

M3 - Article

C2 - 32139696

SN - 2041-1723

VL - 11

SP - 1217

JO - Nature Communications

JF - Nature Communications

IS - 1

ER -

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

Abstract

Keywords

UN SDGs

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