Novel breast cancer susceptibility loci under linkage peaks identified in African ancestry consortia
© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissionsoup.com..
BACKGROUND: Expansion of genome-wide association studies across population groups is needed to improve our understanding of shared and unique genetic contributions to breast cancer. We performed association and replication studies guided by a priori linkage findings from African ancestry (AA) relative pairs.
METHODS: We performed fixed-effect inverse-variance weighted meta-analysis under three significant AA breast cancer linkage peaks (3q26-27, 12q22-23, and 16q21-22) in 9241 AA cases and 10 193 AA controls. We examined associations with overall breast cancer as well as estrogen receptor (ER)-positive and negative subtypes (193,132 SNPs). We replicated associations in the African-ancestry Breast Cancer Genetic Consortium (AABCG).
RESULTS: In AA women, we identified two associations on chr12q for overall breast cancer (rs1420647, OR = 1.15, p = 2.50×10-6; rs12322371, OR = 1.14, p = 3.15×10-6), and one for ER-negative breast cancer (rs77006600, OR = 1.67, p = 3.51×10-6). On chr3, we identified two associations with ER-negative disease (rs184090918, OR = 3.70, p = 1.23×10-5; rs76959804, OR = 3.57, p = 1.77×10-5) and on chr16q we identified an association with ER-negative disease (rs34147411, OR = 1.62, p = 8.82×10-6). In the replication study, the chr3 associations were significant and effect sizes were larger (rs184090918, OR: 6.66, 95% CI: 1.43, 31.01; rs76959804, OR: 5.24, 95% CI: 1.70, 16.16).
CONCLUSION: The two chr3 SNPs are upstream to open chromatin ENSR00000710716, a regulatory feature that is actively regulated in mammary tissues, providing evidence that variants in this chr3 region may have a regulatory role in our target organ. Our study provides support for breast cancer variant discovery using prioritization based on linkage evidence.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2024 |
---|---|
Erschienen: |
2024 |
Enthalten in: |
Zur Gesamtaufnahme - volume:33 |
---|---|
Enthalten in: |
Human molecular genetics - 33(2024), 8 vom: 08. Apr., Seite 687-697 |
Sprache: |
Englisch |
---|
Links: |
---|
Themen: |
African ancestry |
---|
Anmerkungen: |
Date Completed 09.04.2024 Date Revised 10.04.2024 published: Print Citation Status MEDLINE |
---|
doi: |
10.1093/hmg/ddae002 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM367543273 |
---|
LEADER | 01000caa a22002652 4500 | ||
---|---|---|---|
001 | NLM367543273 | ||
003 | DE-627 | ||
005 | 20240410232428.0 | ||
007 | cr uuu---uuuuu | ||
008 | 240124s2024 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1093/hmg/ddae002 |2 doi | |
028 | 5 | 2 | |a pubmed24n1371.xml |
035 | |a (DE-627)NLM367543273 | ||
035 | |a (NLM)38263910 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Ochs-Balcom, Heather M |e verfasserin |4 aut | |
245 | 1 | 0 | |a Novel breast cancer susceptibility loci under linkage peaks identified in African ancestry consortia |
264 | 1 | |c 2024 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 09.04.2024 | ||
500 | |a Date Revised 10.04.2024 | ||
500 | |a published: Print | ||
500 | |a Citation Status MEDLINE | ||
520 | |a © The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissionsoup.com. | ||
520 | |a BACKGROUND: Expansion of genome-wide association studies across population groups is needed to improve our understanding of shared and unique genetic contributions to breast cancer. We performed association and replication studies guided by a priori linkage findings from African ancestry (AA) relative pairs | ||
520 | |a METHODS: We performed fixed-effect inverse-variance weighted meta-analysis under three significant AA breast cancer linkage peaks (3q26-27, 12q22-23, and 16q21-22) in 9241 AA cases and 10 193 AA controls. We examined associations with overall breast cancer as well as estrogen receptor (ER)-positive and negative subtypes (193,132 SNPs). We replicated associations in the African-ancestry Breast Cancer Genetic Consortium (AABCG) | ||
520 | |a RESULTS: In AA women, we identified two associations on chr12q for overall breast cancer (rs1420647, OR = 1.15, p = 2.50×10-6; rs12322371, OR = 1.14, p = 3.15×10-6), and one for ER-negative breast cancer (rs77006600, OR = 1.67, p = 3.51×10-6). On chr3, we identified two associations with ER-negative disease (rs184090918, OR = 3.70, p = 1.23×10-5; rs76959804, OR = 3.57, p = 1.77×10-5) and on chr16q we identified an association with ER-negative disease (rs34147411, OR = 1.62, p = 8.82×10-6). In the replication study, the chr3 associations were significant and effect sizes were larger (rs184090918, OR: 6.66, 95% CI: 1.43, 31.01; rs76959804, OR: 5.24, 95% CI: 1.70, 16.16) | ||
520 | |a CONCLUSION: The two chr3 SNPs are upstream to open chromatin ENSR00000710716, a regulatory feature that is actively regulated in mammary tissues, providing evidence that variants in this chr3 region may have a regulatory role in our target organ. Our study provides support for breast cancer variant discovery using prioritization based on linkage evidence | ||
650 | 4 | |a Meta-Analysis | |
650 | 4 | |a Journal Article | |
650 | 4 | |a African ancestry | |
650 | 4 | |a breast cancer | |
650 | 4 | |a fine mapping | |
650 | 4 | |a meta-GWAS | |
700 | 1 | |a Preus, Leah |e verfasserin |4 aut | |
700 | 1 | |a Du, Zhaohui |e verfasserin |4 aut | |
700 | 1 | |a Elston, Robert C |e verfasserin |4 aut | |
700 | 1 | |a Teerlink, Craig C |e verfasserin |4 aut | |
700 | 1 | |a Jia, Guochong |e verfasserin |4 aut | |
700 | 1 | |a Guo, Xingyi |e verfasserin |4 aut | |
700 | 1 | |a Cai, Qiuyin |e verfasserin |4 aut | |
700 | 1 | |a Long, Jirong |e verfasserin |4 aut | |
700 | 1 | |a Ping, Jie |e verfasserin |4 aut | |
700 | 1 | |a Li, Bingshan |e verfasserin |4 aut | |
700 | 1 | |a Stram, Daniel O |e verfasserin |4 aut | |
700 | 1 | |a Shu, Xiao-Ou |e verfasserin |4 aut | |
700 | 1 | |a Sanderson, Maureen |e verfasserin |4 aut | |
700 | 1 | |a Gao, Guimin |e verfasserin |4 aut | |
700 | 1 | |a Ahearn, Thomas |e verfasserin |4 aut | |
700 | 1 | |a Lunetta, Kathryn L |e verfasserin |4 aut | |
700 | 1 | |a Zirpoli, Gary |e verfasserin |4 aut | |
700 | 1 | |a Troester, Melissa A |e verfasserin |4 aut | |
700 | 1 | |a Ruiz-Narváez, Edward A |e verfasserin |4 aut | |
700 | 1 | |a Haddad, Stephen A |e verfasserin |4 aut | |
700 | 1 | |a Figueroa, Jonine |e verfasserin |4 aut | |
700 | 1 | |a John, Esther M |e verfasserin |4 aut | |
700 | 1 | |a Bernstein, Leslie |e verfasserin |4 aut | |
700 | 1 | |a Hu, Jennifer J |e verfasserin |4 aut | |
700 | 1 | |a Ziegler, Regina G |e verfasserin |4 aut | |
700 | 1 | |a Nyante, Sarah |e verfasserin |4 aut | |
700 | 1 | |a Bandera, Elisa V |e verfasserin |4 aut | |
700 | 1 | |a Ingles, Sue A |e verfasserin |4 aut | |
700 | 1 | |a Mancuso, Nicholas |e verfasserin |4 aut | |
700 | 1 | |a Press, Michael F |e verfasserin |4 aut | |
700 | 1 | |a Deming, Sandra L |e verfasserin |4 aut | |
700 | 1 | |a Rodriguez-Gil, Jorge L |e verfasserin |4 aut | |
700 | 1 | |a Yao, Song |e verfasserin |4 aut | |
700 | 1 | |a Ogundiran, Temidayo O |e verfasserin |4 aut | |
700 | 1 | |a Ojengbede, Oladosu |e verfasserin |4 aut | |
700 | 1 | |a Bolla, Manjeet K |e verfasserin |4 aut | |
700 | 1 | |a Dennis, Joe |e verfasserin |4 aut | |
700 | 1 | |a Dunning, Alison M |e verfasserin |4 aut | |
700 | 1 | |a Easton, Douglas F |e verfasserin |4 aut | |
700 | 1 | |a Michailidou, Kyriaki |e verfasserin |4 aut | |
700 | 1 | |a Pharoah, Paul D P |e verfasserin |4 aut | |
700 | 1 | |a Sandler, Dale P |e verfasserin |4 aut | |
700 | 1 | |a Taylor, Jack A |e verfasserin |4 aut | |
700 | 1 | |a Wang, Qin |e verfasserin |4 aut | |
700 | 1 | |a O'Brien, Katie M |e verfasserin |4 aut | |
700 | 1 | |a Weinberg, Clarice R |e verfasserin |4 aut | |
700 | 1 | |a Kitahara, Cari M |e verfasserin |4 aut | |
700 | 1 | |a Blot, William |e verfasserin |4 aut | |
700 | 1 | |a Nathanson, Katherine L |e verfasserin |4 aut | |
700 | 1 | |a Hennis, Anselm |e verfasserin |4 aut | |
700 | 1 | |a Nemesure, Barbara |e verfasserin |4 aut | |
700 | 1 | |a Ambs, Stefan |e verfasserin |4 aut | |
700 | 1 | |a Sucheston-Campbell, Lara E |e verfasserin |4 aut | |
700 | 1 | |a Bensen, Jeannette T |e verfasserin |4 aut | |
700 | 1 | |a Chanock, Stephen J |e verfasserin |4 aut | |
700 | 1 | |a Olshan, Andrew F |e verfasserin |4 aut | |
700 | 1 | |a Ambrosone, Christine B |e verfasserin |4 aut | |
700 | 1 | |a Olopade, Olufunmilayo I |e verfasserin |4 aut | |
700 | 1 | |a The Ghana Breast Health Study Team |e verfasserin |4 aut | |
700 | 1 | |a Conti, David V |e verfasserin |4 aut | |
700 | 1 | |a Palmer, Julie |e verfasserin |4 aut | |
700 | 1 | |a García-Closas, Montserrat |e verfasserin |4 aut | |
700 | 1 | |a Huo, Dezheng |e verfasserin |4 aut | |
700 | 1 | |a Zheng, Wei |e verfasserin |4 aut | |
700 | 1 | |a Haiman, Christopher |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Human molecular genetics |d 1994 |g 33(2024), 8 vom: 08. Apr., Seite 687-697 |w (DE-627)NLM012650358 |x 1460-2083 |7 nnns |
773 | 1 | 8 | |g volume:33 |g year:2024 |g number:8 |g day:08 |g month:04 |g pages:687-697 |
856 | 4 | 0 | |u http://dx.doi.org/10.1093/hmg/ddae002 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 33 |j 2024 |e 8 |b 08 |c 04 |h 687-697 |