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@ARTICLE{Darst:276858,
author = {B. F. Darst and J. Shen and R. K. Madduri and A. A.
Rodriguez and Y. Xiao and X. Sheng and E. J. Saunders and T.
Dadaev and M. N. Brook and T. J. Hoffmann and K. Muir and P.
Wan and L. Le Marchand and L. Wilkens and Y. Wang and J.
Schleutker and R. J. MacInnis and C. Cybulski and D. E. Neal
and B. G. Nordestgaard and S. F. Nielsen and J. Batra and J.
A. Clements and A. P. Cancer BioResource and H. Grönberg
and N. Pashayan and R. C. Travis and J. Y. Park and D.
Albanes and S. Weinstein and L. A. Mucci and D. J. Hunter
and K. L. Penney and C. M. Tangen and R. J. Hamilton and
M.-É. Parent and J. L. Stanford and S. Koutros and A. Wolk
and K. D. Sørensen and W. J. Blot and E. D. Yeboah and J.
E. Mensah and Y.-J. Lu and D. J. Schaid and S. N. Thibodeau
and C. M. West and C. Maier and A. S. Kibel and G.
Cancel-Tassin and F. Menegaux and E. M. John and E. M.
Grindedal and K.-T. Khaw and S. A. Ingles and A. Vega and B.
S. Rosenstein and M. R. Teixeira and M. Kogevinas and L.
Cannon-Albright and C. Huff and L. Multigner and R. Kaneva
and R. J. Leach and H. Brenner$^*$ and A. W. Hsing and R. A.
Kittles and A. B. Murphy and C. J. Logothetis and S. L.
Neuhausen and W. B. Isaacs and B. Nemesure and A. J. Hennis
and J. Carpten and H. Pandha and K. De Ruyck and J. Xu and
A. Razack and S.-H. Teo and L. F. Newcomb and J. H. Fowke
and C. Neslund-Dudas and B. A. Rybicki and M. Gamulin and N.
Usmani and F. Claessens and M. Gago-Dominguez and J. E.
Castelao and P. A. Townsend and D. C. Crawford and G.
Petrovics and G. Casey and M. J. Roobol and J. F. Hu and S.
I. Berndt and S. K. Van Den Eeden and D. F. Easton and S. J.
Chanock and M. B. Cook and F. Wiklund and J. S. Witte and R.
A. Eeles and Z. Kote-Jarai and S. Watya and J. M. Gaziano
and A. C. Justice and D. V. Conti and C. A. Haiman},
collaboration = {N. P. Investigators and C. P. Investigators},
title = {{E}valuating approaches for constructing polygenic risk
scores for prostate cancer in men of {A}frican and
{E}uropean ancestry.},
journal = {The American journal of human genetics},
volume = {110},
number = {7},
issn = {0002-9297},
address = {New York, NY},
publisher = {Elsevier},
reportid = {DKFZ-2023-01170},
pages = {1200-1206},
year = {2023},
note = {2023 Jul 6;110(7):1200-1206},
abstract = {Genome-wide polygenic risk scores (GW-PRSs) have been
reported to have better predictive ability than PRSs based
on genome-wide significance thresholds across numerous
traits. We compared the predictive ability of several GW-PRS
approaches to a recently developed PRS of 269 established
prostate cancer-risk variants from multi-ancestry GWASs and
fine-mapping studies (PRS269). GW-PRS models were trained
with a large and diverse prostate cancer GWAS of 107,247
cases and 127,006 controls that we previously used to
develop the multi-ancestry PRS269. Resulting models were
independently tested in 1,586 cases and 1,047 controls of
African ancestry from the California Uganda Study and 8,046
cases and 191,825 controls of European ancestry from the UK
Biobank and further validated in 13,643 cases and 210,214
controls of European ancestry and 6,353 cases and 53,362
controls of African ancestry from the Million Veteran
Program. In the testing data, the best performing GW-PRS
approach had AUCs of 0.656 $(95\%$ CI = 0.635-0.677) in
African and 0.844 $(95\%$ CI = 0.840-0.848) in European
ancestry men and corresponding prostate cancer ORs of 1.83
$(95\%$ CI = 1.67-2.00) and 2.19 $(95\%$ CI = 2.14-2.25),
respectively, for each SD unit increase in the GW-PRS.
Compared to the GW-PRS, in African and European ancestry
men, the PRS269 had larger or similar AUCs (AUC = 0.679,
$95\%$ CI = 0.659-0.700 and AUC = 0.845, $95\%$ CI =
0.841-0.849, respectively) and comparable prostate cancer
ORs (OR = 2.05, $95\%$ CI = 1.87-2.26 and OR = 2.21, $95\%$
CI = 2.16-2.26, respectively). Findings were similar in the
validation studies. This investigation suggests that current
GW-PRS approaches may not improve the ability to predict
prostate cancer risk compared to the PRS269 developed from
multi-ancestry GWASs and fine-mapping.},
keywords = {African ancestry (Other) / genetics (Other) / genome-wide
polygenic risk score (Other) / health disparities (Other) /
polygenic risk score (Other) / prostate cancer (Other) /
risk modeling (Other)},
cin = {C070 / C120 / HD01},
ddc = {570},
cid = {I:(DE-He78)C070-20160331 / I:(DE-He78)C120-20160331 /
I:(DE-He78)HD01-20160331},
pnm = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
pid = {G:(DE-HGF)POF4-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37311464},
doi = {10.1016/j.ajhg.2023.05.010},
url = {https://inrepo02.dkfz.de/record/276858},
}