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@ARTICLE{Mueller:212495,
author = {S. H. Mueller and A. G. Lai and M. Valkovskaya and K.
Michailidou and M. K. Bolla and Q. Wang and J. Dennis and M.
Lush and Z. Abu-Ful and T. U. Ahearn and I. L. Andrulis and
H. Anton-Culver and N. N. Antonenkova and V. Arndt and K. J.
Aronson and A. Augustinsson and T. Baert and L. E. B.
Freeman and M. W. Beckmann and S. Behrens$^*$ and J. Benitez
and M. Bermisheva and C. Blomqvist and N. V. Bogdanova and
S. E. Bojesen and B. Bonanni and H. Brenner$^*$ and S. Y.
Brucker and S. S. Buys and J. E. Castelao and T. L. Chan and
J. Chang-Claude$^*$ and S. J. Chanock and J.-Y. Choi and W.
K. Chung and S. V. Colonna and S. Cornelissen and F. J.
Couch and K. Czene and M. B. Daly and P. Devilee and T.
Dörk and L. Dossus and M. Dwek and D. M. Eccles and A. B.
Ekici and A. H. Eliassen and C. Engel and D. G. Evans and P.
A. Fasching and O. Fletcher and H. Flyger and M.
Gago-Dominguez and Y.-T. Gao and M. García-Closas and J. A.
García-Sáenz and J. Genkinger and A. Gentry-Maharaj and F.
Grassmann and P. Guénel and M. Gündert$^*$ and L. Haeberle
and E. Hahnen and C. A. Haiman and N. Håkansson and P. Hall
and E. F. Harkness and P. A. Harrington and J. M.
Hartikainen and M. Hartman and A. Hein and W.-K. Ho and M.
J. Hooning and R. Hoppe and J. L. Hopper and R. S. Houlston
and A. Howell and D. J. Hunter and D. Huo and H. Ito and M.
Iwasaki and A. Jakubowska and W. Janni and E. M. John and M.
E. Jones and A. Y. Jung$^*$ and R. Kaaks$^*$ and D. Kang and
E. K. Khusnutdinova and S.-W. Kim and C. M. Kitahara and S.
Koutros and P. Kraft and V. N. Kristensen and K.
Kubelka-Sabit and A. W. Kurian and A. Kwong and J. V. Lacey
and D. Lambrechts and L. Le Marchand and J. Li and M. Linet
and W.-Y. Lo and J. Long and A. Lophatananon and A.
Mannermaa and M. Manoochehri$^*$ and S. Margolin and K.
Matsuo and D. Mavroudis and U. Menon and K. Muir and R. A.
Murphy and H. Nevanlinna and W. G. Newman and D. Niederacher
and K. M. O'Brien and N. Obi and K. Offit and O. I. Olopade
and A. F. Olshan and H. Olsson and S. K. Park and A. V.
Patel and A. Patel and C. M. Perou and J. Peto and P. D. P.
Pharoah and D. Plaseska-Karanfilska and N. Presneau and B.
Rack and P. Radice and D. Ramachandran and M. U. Rashid$^*$
and G. Rennert and A. Romero and K. J. Ruddy and M. Ruebner
and E. Saloustros and D. P. Sandler and E. J. Sawyer and M.
K. Schmidt and R. K. Schmutzler and M. O. Schneider and C.
Scott and M. Shah and P. Sharma and C.-Y. Shen and X.-O. Shu
and J. Simard and H. Surowy and R. M. Tamimi and W. J.
Tapper and J. A. Taylor and S. H. Teo and L. R. Teras and A.
E. Toland and R. A. E. M. Tollenaar and D. Torres$^*$ and G.
Torres-Mejía and M. A. Troester and T. Truong and C. M.
Vachon and J. Vijai and C. R. Weinberg and C. Wendt and R.
Winqvist and A. Wolk and A. H. Wu and T. Yamaji and X. R.
Yang and J.-C. Yu and W. Zheng and A. Ziogas and E. Ziv and
A. M. Dunning and D. F. Easton and H. Hemingway and U.
Hamann$^*$ and K. B. Kuchenbaecker},
collaboration = {NBCS Collaborators and C. Consortium and A. Investigators},
othercontributors = {K. K. Sahlberg and A.-L. Børresen-Dale and L. Ottestad and
R. Kåresen and E. Schlichting and M. M. Holmen and T. Sauer
and V. Haakensen and O. Engebråten and B. Naume and A.
Fosså and C. E. Kiserud and K. V. Reinertsen and Å.
Helland and M. Riis and J. Geisler and G. I. Grenaker Alnaes
and D. Marsh and R. Scott and R. Baxter and D. Yip and J.
Carpenter and A. Davis and N. Pathmanathan and P. Simpson
and D. Graham and M. Sachchithananthan},
title = {{A}ggregation tests identify new gene associations with
breast cancer in populations with diverse ancestry.},
journal = {Genome medicine},
volume = {15},
number = {1},
issn = {1756-994X},
address = {London},
publisher = {BioMed Central},
reportid = {DKFZ-2023-00196},
pages = {7},
year = {2023},
note = {#LA:B070#LA:B072#},
abstract = {Low-frequency variants play an important role in breast
cancer (BC) susceptibility. Gene-based methods can increase
power by combining multiple variants in the same gene and
help identify target genes.We evaluated the potential of
gene-based aggregation in the Breast Cancer Association
Consortium cohorts including 83,471 cases and 59,199
controls. Low-frequency variants were aggregated for
individual genes' coding and regulatory regions. Association
results in European ancestry samples were compared to
single-marker association results in the same cohort.
Gene-based associations were also combined in meta-analysis
across individuals with European, Asian, African, and Latin
American and Hispanic ancestry.In European ancestry samples,
14 genes were significantly associated (q < 0.05) with BC.
Of those, two genes, FMNL3 (P = 6.11 × 10-6) and AC058822.1
(P = 1.47 × 10-4), represent new associations. High FMNL3
expression has previously been linked to poor prognosis in
several other cancers. Meta-analysis of samples with diverse
ancestry discovered further associations including
established candidate genes ESR1 and CBLB. Furthermore,
literature review and database query found further support
for a biologically plausible link with cancer for genes
CBLB, FMNL3, FGFR2, LSP1, MAP3K1, and SRGAP2C.Using extended
gene-based aggregation tests including coding and regulatory
variation, we report identification of plausible target
genes for previously identified single-marker associations
with BC as well as the discovery of novel genes implicated
in BC development. Including multi ancestral cohorts in this
study enabled the identification of otherwise missed disease
associations as ESR1 (P = 1.31 × 10-5), demonstrating the
importance of diversifying study cohorts.},
keywords = {Breast cancer susceptibility (Other) / Diverse ancestry
(Other) / Gene regulation (Other) / Genome-wide association
study (Other) / Rare variants (Other)},
cin = {C070 / C020 / C120 / HD01 / B072 / B070 / C080},
ddc = {610},
cid = {I:(DE-He78)C070-20160331 / I:(DE-He78)C020-20160331 /
I:(DE-He78)C120-20160331 / I:(DE-He78)HD01-20160331 /
I:(DE-He78)B072-20160331 / I:(DE-He78)B070-20160331 /
I:(DE-He78)C080-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36703164},
doi = {10.1186/s13073-022-01152-5},
url = {https://inrepo02.dkfz.de/record/212495},
}