Assessment of polygenic architecture and risk prediction based on common variants across fourteen cancers
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Assessment of polygenic architecture and risk prediction based on common variants across fourteen cancers. / Zhang, Yan Dora; Hurson, Amber N; Zhang, Haoyu; Choudhury, Parichoy Pal; Easton, Douglas F; Milne, Roger L; Simard, Jacques; Hall, Per; Michailidou, Kyriaki; Dennis, Joe; Schmidt, Marjanka K; Chang-Claude, Jenny; Gharahkhani, Puya; Whiteman, David; Campbell, Peter T; Hoffmeister, Michael; Jenkins, Mark; Hsu, Li; Gruber, Stephen B; Casey, Graham; Schmit, Stephanie L; O'Mara, Tracy A; Spurdle, Amanda B; Thompson, Deborah J; Tomlinson, Ian; De Vivo, Immaculata; Landi, Maria Teresa; Law, Matthew H; Iles, Mark M; Demenais, Florence; Kumar, Rajiv; MacGregor, Stuart; Bishop, D Timothy; Ward, Sarah V; Bondy, Melissa L; Houlston, Richard; Wiencke, John K; Melin, Beatrice; Barnholtz-Sloan, Jill; Kinnersley, Ben; Wrensch, Margaret R; Amos, Christopher I; Hung, Rayjean J; Brennan, Paul; McKay, James; Caporaso, Neil E; Berndt, Sonja I; Birmann, Brenda M; Camp, Nicola J; Kraft, Peter; Rothman, Nathaniel; Slager, Susan L; Berchuck, Andrew; Pharoah, Paul D P; Sellers, Thomas A; Gayther, Simon A; Pearce, Celeste L; Goode, Ellen L; Schildkraut, Joellen M; Moysich, Kirsten B; Amundadottir, Laufey T; Jacobs, Eric J; Klein, Alison P; Petersen, Gloria M; Risch, Harvey A; Stolzenberg-Solomon, Rachel Z; Wolpin, Brian M; Li, Donghui; Eeles, Rosalind A; Haiman, Christopher A; Kote-Jarai, Zsofia; Schumacher, Fredrick R; Al Olama, Ali Amin; Purdue, Mark P; Scelo, Ghislaine; Dalgaard, Marlene D; Greene, Mark H; Grotmol, Tom; Kanetsky, Peter A; McGlynn, Katherine A; Nathanson, Katherine L; Turnbull, Clare; Wiklund, Fredrik; Chanock, Stephen J; Chatterjee, Nilanjan; Garcia-Closas, Montserrat; Breast Cancer Association Consortium (BCAC).
In: NAT COMMUN, Vol. 11, No. 1, 03.07.2020, p. 3353.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Assessment of polygenic architecture and risk prediction based on common variants across fourteen cancers
AU - Zhang, Yan Dora
AU - Hurson, Amber N
AU - Zhang, Haoyu
AU - Choudhury, Parichoy Pal
AU - Easton, Douglas F
AU - Milne, Roger L
AU - Simard, Jacques
AU - Hall, Per
AU - Michailidou, Kyriaki
AU - Dennis, Joe
AU - Schmidt, Marjanka K
AU - Chang-Claude, Jenny
AU - Gharahkhani, Puya
AU - Whiteman, David
AU - Campbell, Peter T
AU - Hoffmeister, Michael
AU - Jenkins, Mark
AU - Hsu, Li
AU - Gruber, Stephen B
AU - Casey, Graham
AU - Schmit, Stephanie L
AU - O'Mara, Tracy A
AU - Spurdle, Amanda B
AU - Thompson, Deborah J
AU - Tomlinson, Ian
AU - De Vivo, Immaculata
AU - Landi, Maria Teresa
AU - Law, Matthew H
AU - Iles, Mark M
AU - Demenais, Florence
AU - Kumar, Rajiv
AU - MacGregor, Stuart
AU - Bishop, D Timothy
AU - Ward, Sarah V
AU - Bondy, Melissa L
AU - Houlston, Richard
AU - Wiencke, John K
AU - Melin, Beatrice
AU - Barnholtz-Sloan, Jill
AU - Kinnersley, Ben
AU - Wrensch, Margaret R
AU - Amos, Christopher I
AU - Hung, Rayjean J
AU - Brennan, Paul
AU - McKay, James
AU - Caporaso, Neil E
AU - Berndt, Sonja I
AU - Birmann, Brenda M
AU - Camp, Nicola J
AU - Kraft, Peter
AU - Rothman, Nathaniel
AU - Slager, Susan L
AU - Berchuck, Andrew
AU - Pharoah, Paul D P
AU - Sellers, Thomas A
AU - Gayther, Simon A
AU - Pearce, Celeste L
AU - Goode, Ellen L
AU - Schildkraut, Joellen M
AU - Moysich, Kirsten B
AU - Amundadottir, Laufey T
AU - Jacobs, Eric J
AU - Klein, Alison P
AU - Petersen, Gloria M
AU - Risch, Harvey A
AU - Stolzenberg-Solomon, Rachel Z
AU - Wolpin, Brian M
AU - Li, Donghui
AU - Eeles, Rosalind A
AU - Haiman, Christopher A
AU - Kote-Jarai, Zsofia
AU - Schumacher, Fredrick R
AU - Al Olama, Ali Amin
AU - Purdue, Mark P
AU - Scelo, Ghislaine
AU - Dalgaard, Marlene D
AU - Greene, Mark H
AU - Grotmol, Tom
AU - Kanetsky, Peter A
AU - McGlynn, Katherine A
AU - Nathanson, Katherine L
AU - Turnbull, Clare
AU - Wiklund, Fredrik
AU - Chanock, Stephen J
AU - Chatterjee, Nilanjan
AU - Garcia-Closas, Montserrat
AU - Breast Cancer Association Consortium (BCAC)
PY - 2020/7/3
Y1 - 2020/7/3
N2 - 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.
AB - 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.
KW - Animals
KW - Female
KW - Genetic Predisposition to Disease
KW - Genome-Wide Association Study
KW - Humans
KW - Incidence
KW - Male
KW - Models, Genetic
KW - Multifactorial Inheritance
KW - Neoplasms/epidemiology
KW - Polymorphism, Single Nucleotide
KW - Risk Assessment/methods
KW - Risk Factors
U2 - 10.1038/s41467-020-16483-3
DO - 10.1038/s41467-020-16483-3
M3 - SCORING: Journal article
C2 - 32620889
VL - 11
SP - 3353
JO - NAT COMMUN
JF - NAT COMMUN
SN - 2041-1723
IS - 1
ER -