Assessment of polygenic architecture and risk prediction based on common variants across fourteen cancers.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
03 07 2020
03 07 2020
Historique:
received:
14
09
2019
accepted:
04
05
2020
entrez:
5
7
2020
pubmed:
6
7
2020
medline:
29
8
2020
Statut:
epublish
Résumé
Genome-wide association studies (GWAS) have led to the identification of hundreds of susceptibility loci across cancers, but the impact of further studies remains uncertain. Here we analyse summary-level data from GWAS of European ancestry across fourteen cancer sites to estimate the number of common susceptibility variants (polygenicity) and underlying effect-size distribution. All cancers show a high degree of polygenicity, involving at a minimum of thousands of loci. We project that sample sizes required to explain 80% of GWAS heritability vary from 60,000 cases for testicular to over 1,000,000 cases for lung cancer. The maximum relative risk achievable for subjects at the 99th risk percentile of underlying polygenic risk scores (PRS), compared to average risk, ranges from 12 for testicular to 2.5 for ovarian cancer. We show that PRS have potential for risk stratification for cancers of breast, colon and prostate, but less so for others because of modest heritability and lower incidence.
Identifiants
pubmed: 32620889
doi: 10.1038/s41467-020-16483-3
pii: 10.1038/s41467-020-16483-3
pmc: PMC7335068
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
3353Subventions
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : NHGRI NIH HHS
ID : R01 HG010480
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA062924
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA164947
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA206110
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA167551
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA207360
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA154823
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA127001
Pays : United States
Organisme : Cancer Research UK
ID : 10589
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : R01 CA197350
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES013508
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA081488
Pays : United States
Investigateurs
Douglas F Easton
(DF)
Roger L Milne
(RL)
Jacques Simard
(J)
Per Hall
(P)
Kyriaki Michailidou
(K)
Joe Dennis
(J)
Marjanka K Schmidt
(MK)
Jenny Chang-Claude
(J)
Puya Gharahkhani
(P)
David Whiteman
(D)
Peter T Campbell
(PT)
Michael Hoffmeister
(M)
Mark Jenkins
(M)
Ulrike Peters
(U)
Li Hsu
(L)
Stephen B Gruber
(SB)
Graham Casey
(G)
Stephanie L Schmit
(SL)
Peter T Campbell
(PT)
Michael Hoffmeister
(M)
Mark Jenkins
(M)
Ulrike Peters
(U)
Li Hsu
(L)
Stephen B Gruber
(SB)
Graham Casey
(G)
Stephanie L Schmit
(SL)
Tracy A O'Mara
(TA)
Amanda B Spurdle
(AB)
Deborah J Thompson
(DJ)
Ian Tomlinson
(I)
Immaculata De Vivo
(I)
Peter T Campbell
(PT)
Michael Hoffmeister
(M)
Mark Jenkins
(M)
Ulrike Peters
(U)
Li Hsu
(L)
Stephen B Gruber
(SB)
Graham Casey
(G)
Stephanie L Schmit
(SL)
Maria Teresa Landi
(MT)
Matthew H Law
(MH)
Mark M Iles
(MM)
Florence Demenais
(F)
Rajiv Kumar
(R)
Stuart MacGregor
(S)
David T Bishop
(DT)
Sarah V Ward
(SV)
Melissa L Bondy
(ML)
Richard Houlston
(R)
John K Wiencke
(JK)
Beatrice Melin
(B)
Jill Barnholtz-Sloan
(J)
Ben Kinnersley
(B)
Margaret R Wrensch
(MR)
Christopher I Amos
(CI)
Rayjean J Hung
(RJ)
Paul Brennan
(P)
James McKay
(J)
Neil E Caporaso
(NE)
Christopher I Amos
(CI)
Rayjean J Hung
(RJ)
Paul Brennan
(P)
James McKay
(J)
Neil E Caporaso
(NE)
Sonja I Berndt
(SI)
Brenda M Birmann
(BM)
Nicola J Camp
(NJ)
Peter Kraft
(P)
Nathaniel Rothman
(N)
Susan L Slager
(SL)
Andrew Berchuck
(A)
Paul D P Pharoah
(PDP)
Thomas A Sellers
(TA)
Simon A Gayther
(SA)
Celeste L Pearce
(CL)
Ellen L Goode
(EL)
Joellen M Schildkraut
(JM)
Kirsten B Moysich
(KB)
Christopher I Amos
(CI)
Paul Brennan
(P)
James McKay
(J)
Laufey T Amundadottir
(LT)
Eric J Jacobs
(EJ)
Alison P Klein
(AP)
Gloria M Petersen
(GM)
Harvey A Risch
(HA)
Rachel Z Stolzenberg-Solomon
(RZ)
Brian M Wolpin
(BM)
Donghui Li
(D)
Laufey T Amundadottir
(LT)
Eric J Jacobs
(EJ)
Alison P Klein
(AP)
Gloria M Petersen
(GM)
Harvey A Risch
(HA)
Rachel Z Stolzenberg-Solomon
(RZ)
Brian M Wolpin
(BM)
Donghui Li
(D)
Rosalind A Eeles
(RA)
Christopher A Haiman
(CA)
Zsofia Kote-Jarai
(Z)
Fredrick R Schumacher
(FR)
Ali Amin Al Olama
(AA)
Mark P Purdue
(MP)
Ghislaine Scelo
(G)
Marlene D Dalgaard
(MD)
Mark H Greene
(MH)
Tom Grotmol
(T)
Peter A Kanetsky
(PA)
Katherine A McGlynn
(KA)
Katherine L Nathanson
(KL)
Clare Turnbull
(C)
Fredrik Wiklund
(F)
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