Testing the generalizability of ancestry-specific polygenic risk scores to predict prostate cancer in sub-Saharan Africa.
Testing the generalizability of ancestry-specific polygenic risk scores to predict prostate cancer in sub-Saharan Africa.
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DOI：
10.1186/s13059-022-02766-z
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发表时间：
2022-09-13
期刊：
影响因子：
12.3
通讯作者：
中科院分区：
文献类型：
--
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全基因组关联研究并不总是在人群中很好地复制，限制了多基因风险评分(PR)的普遍性。尽管非洲裔男性前列腺癌的发病率和死亡率更高，但人们对癌症遗传学的大部分了解都来自欧洲裔人群。为了了解基因预测在不同人群中的表现如何，我们使用来自英国生物库的数据和来自加纳、尼日利亚、塞内加尔和南非的1298例前列腺癌病例和1333名对照的新数据集，评估了之前三项研究中的PRS的测试特征。等位基因频率的差异导致前列腺癌的预测风险因人群而异。然而，自然选择并不是造成这些差异的主要原因。比较欧洲大陆的数据集，我们发现病例与控制状态的多基因预测对欧洲人(AuC 0.608-0.707，OR2.37-5.71)比非洲人(AuC 0.502-0.585，OR0.95-2.01)更有效。此外，利用来自非裔美国人的信息的PR可为撒哈拉以南非洲个人带来适度的AUC和赔率比改善。对西非人来说，这些改善比对南非人更大。最后，我们发现，现有的PR在很大程度上无法预测非洲人是否会患上侵袭性前列腺癌，如较高的肿瘤分期或Gleason评分所指定的。如果研究样本与原始GWA的祖先不匹配，前列腺癌的遗传预测效果很差。从欧洲GWAS建立的PR可能不适合在非欧洲人群中应用，并使现有的健康差距永久化。网上版载有补充材料，可在10.1186/s13059-022-02766-z查阅。
Genome-wide association studies do not always replicate well across populations, limiting the generalizability of polygenic risk scores (PRS). Despite higher incidence and mortality rates of prostate cancer in men of African descent, much of what is known about cancer genetics comes from populations of European descent. To understand how well genetic predictions perform in different populations, we evaluated test characteristics of PRS from three previous studies using data from the UK Biobank and a novel dataset of 1298 prostate cancer cases and 1333 controls from Ghana, Nigeria, Senegal, and South Africa. Allele frequency differences cause predicted risks of prostate cancer to vary across populations. However, natural selection is not the primary driver of these differences. Comparing continental datasets, we find that polygenic predictions of case vs. control status are more effective for European individuals (AUC 0.608–0.707, OR 2.37–5.71) than for African individuals (AUC 0.502–0.585, OR 0.95–2.01). Furthermore, PRS that leverage information from African Americans yield modest AUC and odds ratio improvements for sub-Saharan African individuals. These improvements were larger for West Africans than for South Africans. Finally, we find that existing PRS are largely unable to predict whether African individuals develop aggressive forms of prostate cancer, as specified by higher tumor stages or Gleason scores. Genetic predictions of prostate cancer perform poorly if the study sample does not match the ancestry of the original GWAS. PRS built from European GWAS may be inadequate for application in non-European populations and perpetuate existing health disparities. The online version contains supplementary material available at 10.1186/s13059-022-02766-z.
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影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
影响因子：
14.9
作者：
Buniello, Annalisa;MacArthur, Jacqueline A. L.;Parkinson, Helen
通讯作者：
Parkinson, Helen
影响因子：
2.8
作者：
Beebe-Dimmer, Jennifer L.;Zuhlke, Kimberly A.;Cooney, Kathleen A.
通讯作者：
Cooney, Kathleen A.
跨务基因组全基因组关联的前列腺癌荟萃分析确定了新的敏感性基因座并告知遗传风险预测。
影响因子：
30.8
作者：
Conti DV;Darst BF;Moss LC;Saunders EJ;Sheng X;Chou A;Schumacher FR;Olama AAA;Benlloch S;Dadaev T;Brook MN;Sahimi A;Hoffmann TJ;Takahashi A;Matsuda K;Momozawa Y;Fujita M;Muir K;Lophatananon A;Wan P;Le Marchand L;Wilkens LR;Stevens VL;Gapstur SM;Carter BD;Schleutker J;Tammela TLJ;Sipeky C;Auvinen A;Giles GG;Southey MC;MacInnis RJ;Cybulski C;Wokołorczyk D;Lubiński J;Neal DE;Donovan JL;Hamdy FC;Martin RM;Nordestgaard BG;Nielsen SF;Weischer M;Bojesen SE;Røder MA;Iversen P;Batra J;Chambers S;Moya L;Horvath L;Clements JA;Tilley W;Risbridger GP;Gronberg H;Aly M;Szulkin R;Eklund M;Nordström T;Pashayan N;Dunning AM;Ghoussaini M;Travis RC;Key TJ;Riboli E;Park JY;Sellers TA;Lin HY;Albanes D;Weinstein SJ;Mucci LA;Giovannucci E;Lindstrom S;Kraft P;Hunter DJ;Penney KL;Turman C;Tangen CM;Goodman PJ;Thompson IM Jr;Hamilton RJ;Fleshner NE;Finelli A;Parent MÉ;Stanford JL;Ostrander EA;Geybels MS;Koutros S;Freeman LEB;Stampfer M;Wolk A;Håkansson N;Andriole GL;Hoover RN;Machiela MJ;Sørensen KD;Borre M;Blot WJ;Zheng W;Yeboah ED;Mensah JE;Lu YJ;Zhang HW;Feng N;Mao X;Wu Y;Zhao SC;Sun Z;Thibodeau SN;McDonnell SK;Schaid DJ;West CML;Burnet N;Barnett G;Maier C;Schnoeller T;Luedeke M;Kibel AS;Drake BF;Cussenot O;Cancel-Tassin G;Menegaux F;Truong T;Koudou YA;John EM;Grindedal EM;Maehle L;Khaw KT;Ingles SA;Stern MC;Vega A;Gómez-Caamaño A;Fachal L;Rosenstein BS;Kerns SL;Ostrer H;Teixeira MR;Paulo P;Brandão A;Watya S;Lubwama A;Bensen JT;Fontham ETH;Mohler J;Taylor JA;Kogevinas M;Llorca J;Castaño-Vinyals G;Cannon-Albright L;Teerlink CC;Huff CD;Strom SS;Multigner L;Blanchet P;Brureau L;Kaneva R;Slavov C;Mitev V;Leach RJ;Weaver B;Brenner H;Cuk K;Holleczek B;Saum KU;Klein EA;Hsing AW;Kittles RA;Murphy AB;Logothetis CJ;Kim J;Neuhausen SL;Steele L;Ding YC;Isaacs WB;Nemesure B;Hennis AJM;Carpten J;Pandha H;Michael A;De Ruyck K;De Meerleer G;Ost P;Xu J;Razack A;Lim J;Teo SH;Newcomb LF;Lin DW;Fowke JH;Neslund-Dudas C;Rybicki BA;Gamulin M;Lessel D;Kulis T;Usmani N;Singhal S;Parliament M;Claessens F;Joniau S;Van den Broeck T;Gago-Dominguez M;Castelao JE;Martinez ME;Larkin S;Townsend PA;Aukim-Hastie C;Bush WS;Aldrich MC;Crawford DC;Srivastava S;Cullen JC;Petrovics G;Casey G;Roobol MJ;Jenster G;van Schaik RHN;Hu JJ;Sanderson M;Varma R;McKean-Cowdin R;Torres M;Mancuso N;Berndt SI;Van Den Eeden SK;Easton DF;Chanock SJ;Cook MB;Wiklund F;Nakagawa H;Witte JS;Eeles RA;Kote-Jarai Z;Haiman CA
通讯作者：
Haiman CA
影响因子：
3.7
作者：
Geibel J;Reimer C;Weigend S;Weigend A;Pook T;Simianer H
通讯作者：
Simianer H