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1. Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry

Author

Graff, Mariaelisa, Justice, Anne E., Young, Kristin L., Marouli, Eirini, Zhang, Xinruo, Fine, Rebecca S., Lim, Elise, Buchanan, Victoria, Rand, Kristin, Feitosa, Mary F., Wojczynski, Mary K., Yanek, Lisa R., Shao, Yaming, Rohde, Rebecca, Adeyemo, Adebowale A., Aldrich, Melinda C., Allison, Matthew A., Ambrosone, Christine B., Ambs, Stefan, Amos, Christopher, Arnett, Donna K., Atwood, Larry, Bandera, Elisa V., Bartz, Traci, Becker, Diane M., Berndt, Sonja I., Bernstein, Leslie, Bielak, Lawrence F., Blot, William J., Bottinger, Erwin P., Bowden, Donald W., Bradfield, Jonathan P., Brody, Jennifer A., Broeckel, Ulrich, Burke, Gregory, Cade, Brian E., Cai, Qiuyin, Caporaso, Neil, Carlson, Chris, Carpten, John, Casey, Graham, Chanock, Stephen J., Chen, Guanjie, Chen, Minhui, Chen, Yii-Der I., Chen, Wei-Min, Chesi, Alessandra, Chiang, Charleston W.K., Chu, Lisa, Coetzee, Gerry A., Conti, David V., Cooper, Richard S., Cushman, Mary, Demerath, Ellen, Deming, Sandra L., Dimitrov, Latchezar, Ding, Jingzhong, Diver, W. Ryan, Duan, Qing, Evans, Michele K., Falusi, Adeyinka G., Faul, Jessica D., Fornage, Myriam, Fox, Caroline, Freedman, Barry I., Garcia, Melissa, Gillanders, Elizabeth M., Goodman, Phyllis, Gottesman, Omri, Grant, Struan F.A., Guo, Xiuqing, Hakonarson, Hakon, Haritunians, Talin, Harris, Tamara B., Harris, Curtis C., Henderson, Brian E., Hennis, Anselm, Hernandez, Dena G., Hirschhorn, Joel N., McNeill, Lorna Haughton, Howard, Timothy D., Howard, Barbara, Hsing, Ann W., Hsu, Yu-Han H., Hu, Jennifer J., Huff, Chad D., Huo, Dezheng, Ingles, Sue A., Irvin, Marguerite R., John, Esther M., Johnson, Karen C., Jordan, Joanne M., Kabagambe, Edmond K., Kang, Sun J., Kardia, Sharon L., Keating, Brendan J., Kittles, Rick A., Klein, Eric A., Kolb, Suzanne, Kolonel, Laurence N., Kooperberg, Charles, Kuller, Lewis, Kutlar, Abdullah, Lange, Leslie, Langefeld, Carl D., Le Marchand, Loic, Leonard, Hampton, Lettre, Guillaume, Levin, Albert M., Li, Yun, Li, Jin, Liu, Yongmei, Liu, Youfang, Liu, Simin, Lohman, Kurt, Lotay, Vaneet, Lu, Yingchang, Maixner, William, Manson, JoAnn E., McKnight, Barbara, Meng, Yan, Monda, Keri L., Monroe, Kris, Moore, Jason H., Mosley, Thomas H., Mudgal, Poorva, Murphy, Adam B., Nadukuru, Rajiv, Nalls, Mike A., Nathanson, Katherine L., Nayak, Uma, N’Diaye, Amidou, Nemesure, Barbara, Neslund-Dudas, Christine, Neuhouser, Marian L., Nyante, Sarah, Ochs-Balcom, Heather, Ogundiran, Temidayo O., Ogunniyi, Adesola, Ojengbede, Oladosu, Okut, Hayrettin, Olopade, Olufunmilayo I., Olshan, Andrew, Padhukasahasram, Badri, Palmer, Julie, Palmer, Cameron D., Palmer, Nicholette D., Papanicolaou, George, Patel, Sanjay R., Pettaway, Curtis A., Peyser, Patricia A., Press, Michael F., Rao, D.C., Rasmussen-Torvik, Laura J., Redline, Susan, Reiner, Alex P., Rhie, Suhn K., Rodriguez-Gil, Jorge L., Rotimi, Charles N., Rotter, Jerome I., Ruiz-Narvaez, Edward A., Rybicki, Benjamin A., Salako, Babatunde, Sale, Michele M., Sanderson, Maureen, Schadt, Eric, Schreiner, Pamela J., Schurmann, Claudia, Schwartz, Ann G., Shriner, Daniel A., Signorello, Lisa B., Singleton, Andrew B., Siscovick, David S., Smith, Jennifer A., Smith, Shad, Speliotes, Elizabeth, Spitz, Margaret, Stanford, Janet L., Stevens, Victoria L., Stram, Alex, Strom, Sara S., Sucheston, Lara, Sun, Yan V., Tajuddin, Salman M., Taylor, Herman, Taylor, Kira, Tayo, Bamidele O., Thun, Michael J., Tucker, Margaret A., Vaidya, Dhananjay, Van Den Berg, David J., Vedantam, Sailaja, Vitolins, Mara, Wang, Zhaoming, Ware, Erin B., Wassertheil-Smoller, Sylvia, Weir, David R., Wiencke, John K., Williams, Scott M., Williams, L. Keoki, Wilson, James G., Witte, John S., Wrensch, Margaret, Wu, Xifeng, Yao, Jie, Zakai, Neil, Zanetti, Krista, Zemel, Babette S., Zhao, Wei, Zhao, Jing Hua, Zheng, Wei, Zhi, Degui, Zhou, Jie, Zhu, Xiaofeng, Ziegler, Regina G., Zmuda, Joe, Zonderman, Alan B., Psaty, Bruce M., Borecki, Ingrid B., Cupples, L. Adrienne, Liu, Ching-Ti, Haiman, Christopher A., Loos, Ruth, Ng, Maggie C.Y., and North, Kari E.

Published
2021
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2. Two Novel Susceptibility Loci for Prostate Cancer in Men of African Ancestry

Author

Conti, David V, Wang, Kan, Sheng, Xin, Bensen, Jeannette T, Hazelett, Dennis J, Cook, Michael B, Ingles, Sue A, Kittles, Rick A, Strom, Sara S, Rybicki, Benjamin A, Nemesure, Barbara, Isaacs, William B, Stanford, Janet L, Zheng, Wei, Sanderson, Maureen, John, Esther M, Park, Jong Y, Xu, Jianfeng, Stevens, Victoria L, Berndt, Sonja I, Huff, Chad D, Wang, Zhaoming, Yeboah, Edward D, Tettey, Yao, Biritwum, Richard B, Adjei, Andrew A, Tay, Evelyn, Truelove, Ann, Niwa, Shelley, Sellers, Thomas A, Yamoah, Kosj, Murphy, Adam B, Crawford, Dana C, Gapstur, Susan M, Bush, William S, Aldrich, Melinda C, Cussenot, Olivier, Petrovics, Gyorgy, Cullen, Jennifer, Neslund-Dudas, Christine, Stern, Mariana C, Jarai, Zsofia-Kote, Govindasami, Koveela, Chokkalingam, Anand P, Hsing, Ann W, Goodman, Phyllis J, Hoffmann, Thomas, Drake, Bettina F, Hu, Jennifer J, Clark, Peter E, Van Den Eeden, Stephen K, Blanchet, Pascal, Fowke, Jay H, Casey, Graham, Hennis, Anselm JM, Han, Ying, Lubwama, Alexander, Thompson, Ian M, Leach, Robin, Easton, Douglas F, Schumacher, Fredrick, Van den Berg, David J, Gundell, Susan M, Stram, Alex, Wan, Peggy, Xia, Lucy, Pooler, Loreall C, Mohler, James L, Fontham, Elizabeth TH, Smith, Gary J, Taylor, Jack A, Srivastava, Shiv, Eeles, Rosalind A, Carpten, John, Kibel, Adam S, Multigner, Luc, Parent, Marie-Elise, Menegaux, Florence, Cancel-Tassin, Geraldine, Klein, Eric A, Brureau, Laurent, Stram, Daniel O, Watya, Stephen, Chanock, Stephen J, Witte, John S, Blot, William J, Henderson, Brian E, and Haiman, Christopher A

Subjects
Aging, Human Genome, Cancer, Prevention, Prostate Cancer, Biotechnology, Clinical Research, Genetics, Urologic Diseases, 2.1 Biological and endogenous factors, Aetiology, Blacks, Case-Control Studies, Checkpoint Kinase 2, Chromosomes, Human, Pair 13, Chromosomes, Human, Pair 22, Gene Frequency, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Insulin Receptor Substrate Proteins, Male, Polymorphism, Single Nucleotide, Prostatic Neoplasms, PRACTICAL/ELLIPSE Consortium, Black People, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

Prostate cancer incidence is 1.6-fold higher in African Americans than in other populations. The risk factors that drive this disparity are unknown and potentially consist of social, environmental, and genetic influences. To investigate the genetic basis of prostate cancer in men of African ancestry, we performed a genome-wide association meta-analysis using two-sided statistical tests in 10 202 case subjects and 10 810 control subjects. We identified novel signals on chromosomes 13q34 and 22q12, with the risk-associated alleles found only in men of African ancestry (13q34: rs75823044, risk allele frequency = 2.2%, odds ratio [OR] = 1.55, 95% confidence interval [CI] = 1.37 to 1.76, P = 6.10 × 10-12; 22q12.1: rs78554043, risk allele frequency = 1.5%, OR = 1.62, 95% CI = 1.39 to 1.89, P = 7.50 × 10-10). At 13q34, the signal is located 5' of the gene IRS2 and 3' of a long noncoding RNA, while at 22q12 the candidate functional allele is a missense variant in the CHEK2 gene. These findings provide further support for the role of ancestry-specific germline variation in contributing to population differences in prostate cancer risk.

Published
2017

3. Discovery and fine-mapping of adiposity loci using high density imputation of genome-wide association studies in individuals of African ancestry: African Ancestry Anthropometry Genetics Consortium.

Author

Ng, Maggie CY, Graff, Mariaelisa, Lu, Yingchang, Justice, Anne E, Mudgal, Poorva, Liu, Ching-Ti, Young, Kristin, Yanek, Lisa R, Feitosa, Mary F, Wojczynski, Mary K, Rand, Kristin, Brody, Jennifer A, Cade, Brian E, Dimitrov, Latchezar, Duan, Qing, Guo, Xiuqing, Lange, Leslie A, Nalls, Michael A, Okut, Hayrettin, Tajuddin, Salman M, Tayo, Bamidele O, Vedantam, Sailaja, Bradfield, Jonathan P, Chen, Guanjie, Chen, Wei-Min, Chesi, Alessandra, Irvin, Marguerite R, Padhukasahasram, Badri, Smith, Jennifer A, Zheng, Wei, Allison, Matthew A, Ambrosone, Christine B, Bandera, Elisa V, Bartz, Traci M, Berndt, Sonja I, Bernstein, Leslie, Blot, William J, Bottinger, Erwin P, Carpten, John, Chanock, Stephen J, Chen, Yii-Der Ida, Conti, David V, Cooper, Richard S, Fornage, Myriam, Freedman, Barry I, Garcia, Melissa, Goodman, Phyllis J, Hsu, Yu-Han H, Hu, Jennifer, Huff, Chad D, Ingles, Sue A, John, Esther M, Kittles, Rick, Klein, Eric, Li, Jin, McKnight, Barbara, Nayak, Uma, Nemesure, Barbara, Ogunniyi, Adesola, Olshan, Andrew, Press, Michael F, Rohde, Rebecca, Rybicki, Benjamin A, Salako, Babatunde, Sanderson, Maureen, Shao, Yaming, Siscovick, David S, Stanford, Janet L, Stevens, Victoria L, Stram, Alex, Strom, Sara S, Vaidya, Dhananjay, Witte, John S, Yao, Jie, Zhu, Xiaofeng, Ziegler, Regina G, Zonderman, Alan B, Adeyemo, Adebowale, Ambs, Stefan, Cushman, Mary, Faul, Jessica D, Hakonarson, Hakon, Levin, Albert M, Nathanson, Katherine L, Ware, Erin B, Weir, David R, Zhao, Wei, Zhi, Degui, Bone Mineral Density in Childhood Study (BMDCS) Group, Arnett, Donna K, Grant, Struan FA, Kardia, Sharon LR, Oloapde, Olufunmilayo I, Rao, DC, Rotimi, Charles N, Sale, Michele M, Williams, L Keoki, Zemel, Babette S, Becker, Diane M, and Borecki, Ingrid B

Subjects
Bone Mineral Density in Childhood Study (BMDCS) Group, Humans, Obesity, Genetic Predisposition to Disease, Serine Endopeptidases, Anthropometry, Body Mass Index, Waist-Hip Ratio, Chromosome Mapping, Gene Frequency, Linkage Disequilibrium, Polymorphism, Single Nucleotide, African Continental Ancestry Group, European Continental Ancestry Group, Female, Male, Adiposity, Genome-Wide Association Study, Transcription Factor 7-Like 2 Protein, Genetics, Human Genome, 2.1 Biological and endogenous factors, Developmental Biology
Abstract

Genome-wide association studies (GWAS) have identified >300 loci associated with measures of adiposity including body mass index (BMI) and waist-to-hip ratio (adjusted for BMI, WHRadjBMI), but few have been identified through screening of the African ancestry genomes. We performed large scale meta-analyses and replications in up to 52,895 individuals for BMI and up to 23,095 individuals for WHRadjBMI from the African Ancestry Anthropometry Genetics Consortium (AAAGC) using 1000 Genomes phase 1 imputed GWAS to improve coverage of both common and low frequency variants in the low linkage disequilibrium African ancestry genomes. In the sex-combined analyses, we identified one novel locus (TCF7L2/HABP2) for WHRadjBMI and eight previously established loci at P < 5×10-8: seven for BMI, and one for WHRadjBMI in African ancestry individuals. An additional novel locus (SPRYD7/DLEU2) was identified for WHRadjBMI when combined with European GWAS. In the sex-stratified analyses, we identified three novel loci for BMI (INTS10/LPL and MLC1 in men, IRX4/IRX2 in women) and four for WHRadjBMI (SSX2IP, CASC8, PDE3B and ZDHHC1/HSD11B2 in women) in individuals of African ancestry or both African and European ancestry. For four of the novel variants, the minor allele frequency was low (

Published
2017

4. A Meta-analysis of Multiple Myeloma Risk Regions in African and European Ancestry Populations Identifies Putatively Functional Loci

Author

Rand, Kristin A, Song, Chi, Dean, Eric, Serie, Daniel J, Curtin, Karen, Sheng, Xin, Hu, Donglei, Huff, Carol Ann, Bernal-Mizrachi, Leon, Tomasson, Michael H, Ailawadhi, Sikander, Singhal, Seema, Pawlish, Karen, Peters, Edward S, Bock, Cathryn H, Stram, Alex, Van Den Berg, David J, Edlund, Christopher K, Conti, David V, Zimmerman, Todd, Hwang, Amie E, Huntsman, Scott, Graff, John, Nooka, Ajay, Kong, Yinfei, Pregja, Silvana L, Berndt, Sonja I, Blot, William J, Carpten, John, Casey, Graham, Chu, Lisa, Diver, W Ryan, Stevens, Victoria L, Lieber, Michael R, Goodman, Phyllis J, Hennis, Anselm JM, Hsing, Ann W, Mehta, Jayesh, Kittles, Rick A, Kolb, Suzanne, Klein, Eric A, Leske, Cristina, Murphy, Adam B, Nemesure, Barbara, Neslund-Dudas, Christine, Strom, Sara S, Vij, Ravi, Rybicki, Benjamin A, Stanford, Janet L, Signorello, Lisa B, Witte, John S, Ambrosone, Christine B, Bhatti, Parveen, John, Esther M, Bernstein, Leslie, Zheng, Wei, Olshan, Andrew F, Hu, Jennifer J, Ziegler, Regina G, Nyante, Sarah J, Bandera, Elisa V, Birmann, Brenda M, Ingles, Sue A, Press, Michael F, Atanackovic, Djordje, Glenn, Martha J, Cannon-Albright, Lisa A, Jones, Brandt, Tricot, Guido, Martin, Thomas G, Kumar, Shaji K, Wolf, Jeffrey L, Deming Halverson, Sandra L, Rothman, Nathaniel, Brooks-Wilson, Angela R, Rajkumar, S Vincent, Kolonel, Laurence N, Chanock, Stephen J, Slager, Susan L, Severson, Richard K, Janakiraman, Nalini, Terebelo, Howard R, Brown, Elizabeth E, De Roos, Anneclaire J, Mohrbacher, Ann F, Colditz, Graham A, Giles, Graham G, Spinelli, John J, Chiu, Brian C, Munshi, Nikhil C, Anderson, Kenneth C, Levy, Joan, Zonder, Jeffrey A, Orlowski, Robert Z, Lonial, Sagar, Camp, Nicola J, Vachon, Celine M, Ziv, Elad, Stram, Daniel O, and Hazelett, Dennis J

Subjects
Biomedical and Clinical Sciences, Cancer, Clinical Research, Genetics, Rare Diseases, Hematology, Human Genome, Aetiology, 2.1 Biological and endogenous factors, Adult, Aged, Black People, Female, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Middle Aged, Multiple Myeloma, Polycomb Repressive Complex 1, Polymorphism, Single Nucleotide, Protein Serine-Threonine Kinases, Repressor Proteins, Transmembrane Activator and CAML Interactor Protein, White People, Medical and Health Sciences, Epidemiology, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundGenome-wide association studies (GWAS) in European populations have identified genetic risk variants associated with multiple myeloma.MethodsWe performed association testing of common variation in eight regions in 1,318 patients with multiple myeloma and 1,480 controls of European ancestry and 1,305 patients with multiple myeloma and 7,078 controls of African ancestry and conducted a meta-analysis to localize the signals, with epigenetic annotation used to predict functionality.ResultsWe found that variants in 7p15.3, 17p11.2, 22q13.1 were statistically significantly (P < 0.05) associated with multiple myeloma risk in persons of African ancestry and persons of European ancestry, and the variant in 3p22.1 was associated in European ancestry only. In a combined African ancestry-European ancestry meta-analysis, variation in five regions (2p23.3, 3p22.1, 7p15.3, 17p11.2, 22q13.1) was statistically significantly associated with multiple myeloma risk. In 3p22.1, the correlated variants clustered within the gene body of ULK4 Correlated variants in 7p15.3 clustered around an enhancer at the 3' end of the CDCA7L transcription termination site. A missense variant at 17p11.2 (rs34562254, Pro251Leu, OR, 1.32; P = 2.93 × 10-7) in TNFRSF13B encodes a lymphocyte-specific protein in the TNF receptor family that interacts with the NF-κB pathway. SNPs correlated with the index signal in 22q13.1 cluster around the promoter and enhancer regions of CBX7 CONCLUSIONS: We found that reported multiple myeloma susceptibility regions contain risk variants important across populations, supporting the use of multiple racial/ethnic groups with different underlying genetic architecture to enhance the localization and identification of putatively functional alleles.ImpactA subset of reported risk loci for multiple myeloma has consistent effects across populations and is likely to be functional. Cancer Epidemiol Biomarkers Prev; 25(12); 1609-18. ©2016 AACR.

Published
2016

5. Whole-exome sequencing of over 4100 men of African ancestry and prostate cancer risk

Author

Rand, Kristin A, Rohland, Nadin, Tandon, Arti, Stram, Alex, Sheng, Xin, Do, Ron, Pasaniuc, Bogdan, Allen, Alex, Quinque, Dominique, Mallick, Swapan, Le Marchand, Loic, Kaggwa, Sam, Lubwama, Alex, Stram, Daniel O, Watya, Stephen, Henderson, Brian E, Conti, David V, Reich, David, and Haiman, Christopher A

Subjects
Biological Sciences, Genetics, Clinical Research, Urologic Diseases, Prevention, Human Genome, Aging, Prostate Cancer, Cancer, Aetiology, 2.1 Biological and endogenous factors, Adult, Aged, Black People, Exome, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Prostatic Neoplasms, Risk, Sequence Analysis, DNA, African Ancestry Prostate Cancer GWAS Consortium, ELLIPSE/GAME-ON Consortium, Medical and Health Sciences, Genetics & Heredity
Abstract

Prostate cancer is the most common non-skin cancer in males, with a ∼1.5-2-fold higher incidence in African American men when compared with whites. Epidemiologic evidence supports a large heritable contribution to prostate cancer, with over 100 susceptibility loci identified to date that can explain ∼33% of the familial risk. To explore the contribution of both rare and common variation in coding regions to prostate cancer risk, we sequenced the exomes of 2165 prostate cancer cases and 2034 controls of African ancestry at a mean coverage of 10.1×. We identified 395 220 coding variants down to 0.05% frequency [57% non-synonymous (NS), 42% synonymous and 1% gain or loss of stop codon or splice site variant] in 16 751 genes with the strongest associations observed in SPARCL1 on 4q22.1 (rs13051, Ala49Asp, OR = 0.78, P = 1.8 × 10(-6)) and PTPRR on 12q15 (rs73341069, Val239Ile, OR = 1.62, P = 2.5 × 10(-5)). In gene-level testing, the two most significant genes were C1orf100 (P = 2.2 × 10(-4)) and GORAB (P = 2.3 × 10(-4)). We did not observe exome-wide significant associations (after correcting for multiple hypothesis testing) in single variant or gene-level testing in the overall case-control or case-case analyses of disease aggressiveness. In this first whole-exome sequencing study of prostate cancer, our findings do not provide strong support for the hypothesis that NS coding variants down to 0.5-1.0% frequency have large effects on prostate cancer risk in men of African ancestry. Higher-coverage sequencing efforts in larger samples will be needed to study rarer variants with smaller effect sizes associated with prostate cancer risk.

Published
2016

6. The contribution of rare variation to prostate cancer heritability

Author

Mancuso, Nicholas, Rohland, Nadin, Rand, Kristin A, Tandon, Arti, Allen, Alexander, Quinque, Dominique, Mallick, Swapan, Li, Heng, Stram, Alex, Sheng, Xin, Kote-Jarai, Zsofia, Easton, Douglas F, Eeles, Rosalind A, Le Marchand, Loic, Lubwama, Alex, Stram, Daniel, Watya, Stephen, Conti, David V, Henderson, Brian, Haiman, Christopher A, Pasaniuc, Bogdan, and Reich, David

Subjects
Biological Sciences, Genetics, Prevention, Urologic Diseases, Cancer, Aging, Prostate Cancer, 2.1 Biological and endogenous factors, Aetiology, Aged, Asian People, Black People, Case-Control Studies, Cohort Studies, Female, Gene Frequency, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Prostatic Neoplasms, Uganda, PRACTICAL consortium, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

We report targeted sequencing of 63 known prostate cancer risk regions in a multi-ancestry study of 9,237 men and use the data to explore the contribution of low-frequency variation to disease risk. We show that SNPs with minor allele frequencies (MAFs) of 0.1-1% explain a substantial fraction of prostate cancer risk in men of African ancestry. We estimate that these SNPs account for 0.12 (standard error (s.e.) = 0.05) of variance in risk (∼42% of the variance contributed by SNPs with MAF of 0.1-50%). This contribution is much larger than the fraction of neutral variation due to SNPs in this class, implying that natural selection has driven down the frequency of many prostate cancer risk alleles; we estimate the coupling between selection and allelic effects at 0.48 (95% confidence interval [0.19, 0.78]) under the Eyre-Walker model. Our results indicate that rare variants make a disproportionate contribution to genetic risk for prostate cancer and suggest the possibility that rare variants may also have an outsize effect on other common traits.

Published
2016

7. A comprehensive examination of breast cancer risk loci in African American women

Author

Feng, Ye, Stram, Daniel O., Rhie, Suhn Kyong, Millikan, Robert C., Ambrosone, Christine B., John, Esther M., Bernstein, Leslie, Zheng, Wei, Olshan, Andrew F., Hu, Jennifer J., Ziegler, Regina G., Nyante, Sarah, Bandera, Elisa V., Ingles, Sue A., Press, Michael F., Deming, Sandra L., Rodriguez-Gil, Jorge L., Palmer, Julie R., Olopade, Olufunmilayo I., Huo, Dezheng, Adebamowo, Clement A., Ogundiran, Temidayo, Chen, Gary K., Stram, Alex, Park, Karen, Rand, Kristin A., Chanock, Stephen J., Le Marchand, Loic, Kolonel, Laurence N., Conti, David V., Easton, Douglas, Henderson, Brian E., and Haiman, Christopher A.

Published
2014
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9. Two novel susceptibility loci for prostate cancer in men of African ancestry

Author

Conti, David V., Wang, Kan, Sheng, Xin, Bensen, Jeannette T., Hazelett, Dennis J., Cook, Michael B., Ingles, Sue A., Kittles, Rick A., Strom, Sara S., Rybicki, Benjamin A., Nemesure, Barbara, Isaacs, William B., Stanford, Janet L., Zheng, Wei, Sanderson, Maureen, John, Esther M., Park, Jong Y., Xu, Jianfeng, Stevens, Victoria L., Berndt, Sonja I., Huff, Chad D., Wang, Zhaoming, Yeboah, Edward D., Tettey, Yao, Biritwum, Richard B., Adjei, Andrew A., Tay, Evelyn, Truelove, Ann, Niwa, Shelley, Sellers, Thomas A., Yamoah, Kosj, Murphy, Adam B., Crawford, Dana C., Gapstur, Susan M., Bush, William S., Aldrich, Melinda C., Cussenot, Olivier, Petrovics, Gyorgy, Cullen, Jennifer, Neslund-Dudas, Christine, Stern, Mariana C., Jarai, Zsofia-Kote, Govindasami, Koveela, Chokkalingam, Anand P., Hsing, Ann W., Goodman, Phyllis J., Hoffmann, Thomas, Drake, Bettina F., Hu, Jennifer J., Clark, Peter E., Van Den Eeden, Stephen K., Blanchet, Pascal, Fowke, Jay H., Casey, Graham, Hennis, Anselm J.M., Han, Ying, Lubwama, Alexander, Thompson, Ian M., Leach, Robin, Easton, Douglas F., Schumacher, Fredrick, Van den Berg, David J., Gundell, Susan M., Stram, Alex, Wan, Peggy, Xia, Lucy, Pooler, Loreall C., Mohler, James L., Fontham, Elizabeth T.H., Smith, Gary J., Taylor, Jack A., Srivastava, Shiv, Eeles, Rosalind A., Carpten, John, Kibel, Adam S., Multigner, Luc, Parent, Marie-Elise, Menegaux, Florence, Cancel-Tassin, Geraldine, Klein, Eric A., Brureau, Laurent, Stram, Daniel O., Watya, Stephen, Chanock, Stephen J., Witte, John S., Blot, William J., Henderson, Brian E., Haiman, Christopher A., PRACTICAL/ELLIPSE Consortium, Jyotsna, Conti, David V., Wang, Kan, Sheng, Xin, Bensen, Jeannette T., Hazelett, Dennis J., Cook, Michael B., Ingles, Sue A., Kittles, Rick A., Strom, Sara S., Rybicki, Benjamin A., Nemesure, Barbara, Isaacs, William B., Stanford, Janet L., Zheng, Wei, Sanderson, Maureen, John, Esther M., Park, Jong Y., Xu, Jianfeng, Stevens, Victoria L., Berndt, Sonja I., Huff, Chad D., Wang, Zhaoming, Yeboah, Edward D., Tettey, Yao, Biritwum, Richard B., Adjei, Andrew A., Tay, Evelyn, Truelove, Ann, Niwa, Shelley, Sellers, Thomas A., Yamoah, Kosj, Murphy, Adam B., Crawford, Dana C., Gapstur, Susan M., Bush, William S., Aldrich, Melinda C., Cussenot, Olivier, Petrovics, Gyorgy, Cullen, Jennifer, Neslund-Dudas, Christine, Stern, Mariana C., Jarai, Zsofia-Kote, Govindasami, Koveela, Chokkalingam, Anand P., Hsing, Ann W., Goodman, Phyllis J., Hoffmann, Thomas, Drake, Bettina F., Hu, Jennifer J., Clark, Peter E., Van Den Eeden, Stephen K., Blanchet, Pascal, Fowke, Jay H., Casey, Graham, Hennis, Anselm J.M., Han, Ying, Lubwama, Alexander, Thompson, Ian M., Leach, Robin, Easton, Douglas F., Schumacher, Fredrick, Van den Berg, David J., Gundell, Susan M., Stram, Alex, Wan, Peggy, Xia, Lucy, Pooler, Loreall C., Mohler, James L., Fontham, Elizabeth T.H., Smith, Gary J., Taylor, Jack A., Srivastava, Shiv, Eeles, Rosalind A., Carpten, John, Kibel, Adam S., Multigner, Luc, Parent, Marie-Elise, Menegaux, Florence, Cancel-Tassin, Geraldine, Klein, Eric A., Brureau, Laurent, Stram, Daniel O., Watya, Stephen, Chanock, Stephen J., Witte, John S., Blot, William J., Henderson, Brian E., Haiman, Christopher A., and PRACTICAL/ELLIPSE Consortium, Jyotsna

Abstract

Prostate cancer incidence is 1.6-fold higher in African Americans than in other populations. The risk factors that drive this disparity are unknown and potentially consist of social, environmental, and genetic influences. To investigate the genetic basis of prostate cancer in men of African ancestry, we performed a genome-wide association meta-analysis using two-sided statistical tests in 10 202 case subjects and 10 810 control subjects. We identified novel signals on chromosomes 13q34 and 22q12, with the risk-associated alleles found only in men of African ancestry (13q34: rs75823044, risk allele frequency = 2.2%, odds ratio [OR] = 1.55, 95% confidence interval [CI] = 1.37 to 1.76, P = 6.10 × 10−12; 22q12.1: rs78554043, risk allele frequency = 1.5%, OR = 1.62, 95% CI = 1.39 to 1.89, P = 7.50 × 10−10). At 13q34, the signal is located 5’ of the gene IRS2 and 3’ of a long noncoding RNA, while at 22q12 the candidate functional allele is a missense variant in the CHEK2 gene. These findings provide further support for the role of ancestry-specific germline variation in contributing to population differences in prostate cancer risk.

Published
2017

10. A comprehensive examination of breast cancer risk loci in African American women

Author

Bandera, Elisa V., John, Esther M., Palmer, Julie R., Olshan, Andrew F., Chanock, Stephen J., Ziegler, Regina G., Press, Michael F., Millikan, Robert C., Chen, Gary K., Hu, Jennifer J., Nyante, Sarah, Conti, David V., Ingles, Sue A., Zheng, Wei, Ambrosone, Christine B., Kolonel, Laurence N., Easton, Douglas, Stram, Alex, Park, Karen, Henderson, Brian E., Le Marchand, Loic, Rhie, Suhn Kyong, Ogundiran, Temidayo, Stram, Daniel O., Deming, Sandra L., Rodriguez-Gil, Jorge L., Bernstein, Leslie, Huo, Dezheng, Adebamowo, Clement A., Rand, Kristin A., Feng, Ye, and Olopade, Olufunmilayo I.

Abstract

Genome-wide association studies have identified 73 breast cancer risk variants mainly in European populations. Given considerable differences in linkage disequilibrium structure between populations of European and African ancestry, the known risk variants may not be informative for risk in African ancestry populations. In a previous fine-mapping investigation of 19 breast cancer loci, we were able to identify SNPs in four regions that better captured risk associations in African American women. In this study of breast cancer in African American women (3016 cases, 2745 controls), we tested an additional 54 novel breast cancer risk variants. Thirty-eight variants (70%) were found to have an association with breast cancer in the same direction as previously reported, with eight (15%) replicating at P < 0.05. Through fine-mapping, in three regions (1q32, 3p24, 10q25), we identified variants that better captured associations with overall breast cancer or estrogen receptor positive disease. We also observed suggestive associations with variants (at P < 5 × 10−6) in three separate regions (6q25, 14q13, 22q12) that may represent novel risk variants. Directional consistency of association observed for ∼65–70% of currently known genetic variants for breast cancer in women of African ancestry implies a shared functional common variant at most loci. To validate and enhance the spectrum of alleles that define associations at the known breast cancer risk loci, as well as genome-wide, will require even larger collaborative efforts in women of African ancestry.

Published
2014
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11. A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer

Author

Al Olama, Ali Amin, Kote-Jarai, Zsofia, Berndt, Sonja I, Conti, David V, Schumacher, Fredrick, Han, Ying, Benlloch, Sara, Hazelett, Dennis J, Wang, Zhaoming, Saunders, Ed, Leongamornlert, Daniel, Lindstrom, Sara, Jugurnauth-Little, Sara, Dadaev, Tokhir, Tymrakiewicz, Malgorzata, Stram, Daniel O, Rand, Kristin, Wan, Peggy, Stram, Alex, Sheng, Xin, Pooler, Loreall C, Park, Karen, Xia, Lucy, Tyrer, Jonathan, Kolonel, Laurence N, Le Marchand, Loic, Hoover, Robert N, Machiela, Mitchell J, Yeager, Merideth, Burdette, Laurie, Chung, Charles C, Hutchinson, Amy, Yu, Kai, Goh, Chee, Ahmed, Mahbubl, Govindasami, Koveela, Guy, Michelle, Tammela, Teuvo L J, Auvinen, Anssi, Wahlfors, Tiina, Schleutker, Johanna, Visakorpi, Tapio, Leinonen, Katri A, Xu, Jianfeng, Aly, Markus, Donovan, Jenny, Travis, Ruth C, Key, Tim J, Røder, Martin Andreas, Iversen, Peter, Al Olama, Ali Amin, Kote-Jarai, Zsofia, Berndt, Sonja I, Conti, David V, Schumacher, Fredrick, Han, Ying, Benlloch, Sara, Hazelett, Dennis J, Wang, Zhaoming, Saunders, Ed, Leongamornlert, Daniel, Lindstrom, Sara, Jugurnauth-Little, Sara, Dadaev, Tokhir, Tymrakiewicz, Malgorzata, Stram, Daniel O, Rand, Kristin, Wan, Peggy, Stram, Alex, Sheng, Xin, Pooler, Loreall C, Park, Karen, Xia, Lucy, Tyrer, Jonathan, Kolonel, Laurence N, Le Marchand, Loic, Hoover, Robert N, Machiela, Mitchell J, Yeager, Merideth, Burdette, Laurie, Chung, Charles C, Hutchinson, Amy, Yu, Kai, Goh, Chee, Ahmed, Mahbubl, Govindasami, Koveela, Guy, Michelle, Tammela, Teuvo L J, Auvinen, Anssi, Wahlfors, Tiina, Schleutker, Johanna, Visakorpi, Tapio, Leinonen, Katri A, Xu, Jianfeng, Aly, Markus, Donovan, Jenny, Travis, Ruth C, Key, Tim J, Røder, Martin Andreas, and Iversen, Peter

Abstract

Genome-wide association studies (GWAS) have identified 76 variants associated with prostate cancer risk predominantly in populations of European ancestry. To identify additional susceptibility loci for this common cancer, we conducted a meta-analysis of > 10 million SNPs in 43,303 prostate cancer cases and 43,737 controls from studies in populations of European, African, Japanese and Latino ancestry. Twenty-three new susceptibility loci were identified at association P < 5 × 10(-8); 15 variants were identified among men of European ancestry, 7 were identified in multi-ancestry analyses and 1 was associated with early-onset prostate cancer. These 23 variants, in combination with known prostate cancer risk variants, explain 33% of the familial risk for this disease in European-ancestry populations. These findings provide new regions for investigation into the pathogenesis of prostate cancer and demonstrate the usefulness of combining ancestrally diverse populations to discover risk loci for disease.

Published
2014

12. Abstract 943: A comprehensive examination of breast cancer risk loci in African American women

Author

Feng, Ye, primary, Chen, Gary K., additional, Stram, Daniel O., additional, Millikan, Robert C., additional, Ambrosone, Christine B., additional, John, Esther M., additional, Bernstein, Leslie, additional, Zheng, Wei, additional, Olshan, Andrew F., additional, Hu, Jennifer J., additional, Ziegler, Regina G., additional, Nyante, Sarah, additional, Bandera, Elisa V., additional, Ingles, Sue A., additional, Press, Michael F., additional, Deming, Sandra L., additional, Rodriguez-Gil, Jorge L., additional, Palmer, Julie R., additional, Olopade, Olufunmilayo I., additional, Huo, Dezheng, additional, Adebamowo, Clement A., additional, Ogundiran, Temidayo, additional, Stram, Alex, additional, Park, Karen, additional, Rand, Kristin A., additional, Chanock, Stephen J., additional, Marchand, Loic L., additional, Kolonel, Laurence N., additional, Conti, David V., additional, Easton, Douglas, additional, Henderson, Brian E., additional, and Haiman, Christopher A., additional

Published
2014
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13. Correction: Identification, Replication, and Fine-Mapping of Loci Associated with Adult Height in Individuals of African Ancestry

Author

N'Diaye, Amidou, primary, Chen, Gary K., additional, Palmer, Cameron D., additional, Ge, Bing, additional, Tayo, Bamidele, additional, Mathias, Rasika A., additional, Ding, Jingzhong, additional, Nalls, Michael A., additional, Adeyemo, Adebowale, additional, Adoue, Véronique, additional, Ambrosone, Christine B., additional, Atwood, Larry, additional, Bandera, Elisa V., additional, Becker, Lewis C., additional, Berndt, Sonja I., additional, Bernstein, Leslie, additional, Blot, William J., additional, Boerwinkle, Eric, additional, Britton, Angela, additional, Casey, Graham, additional, Chanock, Stephen J., additional, Demerath, Ellen, additional, Deming, Sandra L., additional, Diver, W. Ryan, additional, Fox, Caroline, additional, Harris, Tamara B., additional, Hernandez, Dena G., additional, Hu, Jennifer J., additional, Ingles, Sue A., additional, John, Esther M., additional, Johnson, Craig, additional, Keating, Brendan, additional, Kittles, Rick A., additional, Kolonel, Laurence N., additional, Kritchevsky, Stephen B., additional, Le Marchand, Loic, additional, Lohman, Kurt, additional, Liu, Jiankang, additional, Millikan, Robert C., additional, Murphy, Adam, additional, Musani, Solomon, additional, Neslund-Dudas, Christine, additional, North, Kari E., additional, Nyante, Sarah, additional, Ogunniyi, Adesola, additional, Ostrander, Elaine A., additional, Papanicolaou, George, additional, Patel, Sanjay, additional, Pettaway, Curtis A., additional, Press, Michael F., additional, Redline, Susan, additional, Rodriguez-Gil, Jorge L., additional, Rotimi, Charles, additional, Rybicki, Benjamin A., additional, Salako, Babatunde, additional, Schreiner, Pamela J., additional, Signorello, Lisa B., additional, Singleton, Andrew B., additional, Stanford, Janet L., additional, Stram, Alex H., additional, Stram, Daniel O., additional, Strom, Sara S., additional, Suktitipat, Bhoom, additional, Thun, Michael J., additional, Witte, John S., additional, Yanek, Lisa R., additional, Ziegler, Regina G., additional, Zheng, Wei, additional, Zhu, Xiaofeng, additional, Zmuda, Joseph M., additional, Zonderman, Alan B., additional, Evans, Michele K., additional, Liu, Yongmei, additional, Becker, Diane M., additional, Cooper, Richard S., additional, Pastinen, Tomi, additional, Henderson, Brian E., additional, Hirschhorn, Joel N., additional, Lettre, Guillaume, additional, and Haiman, Christopher A., additional

Published
2011
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14. Identification, Replication, and Fine-Mapping of Loci Associated with Adult Height in Individuals of African Ancestry

Author

N'Diaye, Amidou, primary, Chen, Gary K., additional, Palmer, Cameron D., additional, Ge, Bing, additional, Tayo, Bamidele, additional, Mathias, Rasika A., additional, Ding, Jingzhong, additional, Nalls, Michael A., additional, Adeyemo, Adebowale, additional, Adoue, Véronique, additional, Ambrosone, Christine B., additional, Atwood, Larry, additional, Bandera, Elisa V., additional, Becker, Lewis C., additional, Berndt, Sonja I., additional, Bernstein, Leslie, additional, Blot, William J., additional, Boerwinkle, Eric, additional, Britton, Angela, additional, Casey, Graham, additional, Chanock, Stephen J., additional, Demerath, Ellen, additional, Deming, Sandra L., additional, Diver, W. Ryan, additional, Fox, Caroline, additional, Harris, Tamara B., additional, Hernandez, Dena G., additional, Hu, Jennifer J., additional, Ingles, Sue A., additional, John, Esther M., additional, Johnson, Craig, additional, Keating, Brendan, additional, Kittles, Rick A., additional, Kolonel, Laurence N., additional, Kritchevsky, Stephen B., additional, Le Marchand, Loic, additional, Lohman, Kurt, additional, Liu, Jiankang, additional, Millikan, Robert C., additional, Murphy, Adam, additional, Musani, Solomon, additional, Neslund-Dudas, Christine, additional, North, Kari E., additional, Nyante, Sarah, additional, Ogunniyi, Adesola, additional, Ostrander, Elaine A., additional, Papanicolaou, George, additional, Patel, Sanjay, additional, Pettaway, Curtis A., additional, Press, Michael F., additional, Redline, Susan, additional, Rodriguez-Gil, Jorge L., additional, Rotimi, Charles, additional, Rybicki, Benjamin A., additional, Salako, Babatunde, additional, Schreiner, Pamela J., additional, Signorello, Lisa B., additional, Singleton, Andrew B., additional, Stanford, Janet L., additional, Stram, Alex H., additional, Stram, Daniel O., additional, Strom, Sara S., additional, Suktitipat, Bhoom, additional, Thun, Michael J., additional, Witte, John S., additional, Yanek, Lisa R., additional, Ziegler, Regina G., additional, Zheng, Wei, additional, Zhu, Xiaofeng, additional, Zmuda, Joseph M., additional, Zonderman, Alan B., additional, Evans, Michele K., additional, Liu, Yongmei, additional, Becker, Diane M., additional, Cooper, Richard S., additional, Pastinen, Tomi, additional, Henderson, Brian E., additional, Hirschhorn, Joel N., additional, Lettre, Guillaume, additional, and Haiman, Christopher A., additional

Published
2011
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15. Discovery and fine-mapping of adiposity loci using high density imputation of genome-wide association studies in individuals of African ancestry: African Ancestry Anthropometry Genetics Consortium

Author

Ng, Maggie C. Y., Graff, Mariaelisa, Lu, Yingchang, Justice, Anne E., Mudgal, Poorva, Liu, Ching-Ti, Young, Kristin, Yanek, Lisa R., Feitosa, Mary F., Wojczynski, Mary K., Rand, Kristin, Brody, Jennifer A., Cade, Brian E., Dimitrov, Latchezar, Duan, Qing, Guo, Xiuqing, Lange, Leslie A., Nalls, Michael A., Okut, Hayrettin, Tajuddin, Salman M., Tayo, Bamidele O., Vedantam, Sailaja, Bradfield, Jonathan P., Chen, Guanjie, Chen, Wei-Min, Chesi, Alessandra, Irvin, Marguerite R., Padhukasahasram, Badri, Smith, Jennifer A., Zheng, Wei, Allison, Matthew A., Ambrosone, Christine B., Bandera, Elisa V., Bartz, Traci M., Berndt, Sonja I., Bernstein, Leslie, Blot, William J., Bottinger, Erwin P., Carpten, John, Chanock, Stephen J., Chen, Yii-Der Ida, Conti, David V., Cooper, Richard S., Fornage, Myriam, Freedman, Barry I., Garcia, Melissa, Goodman, Phyllis J., Hsu, Yu-Han H., Hu, Jennifer, Huff, Chad D., Ingles, Sue A., John, Esther M., Kittles, Rick, Klein, Eric, Li, Jin, McKnight, Barbara, Nayak, Uma, Nemesure, Barbara, Ogunniyi, Adesola, Olshan, Andrew, Press, Michael F., Rohde, Rebecca, Rybicki, Benjamin A., Salako, Babatunde, Sanderson, Maureen, Shao, Yaming, Siscovick, David S., Stanford, Janet L., Stevens, Victoria L., Stram, Alex, Strom, Sara S., Vaidya, Dhananjay, Witte, John S., Yao, Jie, Zhu, Xiaofeng, Ziegler, Regina G., Zonderman, Alan B., Adeyemo, Adebowale, Ambs, Stefan, Cushman, Mary, Faul, Jessica D., Hakonarson, Hakon, Levin, Albert M., Nathanson, Katherine L., Ware, Erin B., Weir, David R., Zhao, Wei, Zhi, Degui, Arnett, Donna K., Grant, Struan F. A., Kardia, Sharon L. R., Oloapde, Olufunmilayo I., Rao, D. C., Rotimi, Charles N., Sale, Michele M., Williams, L. Keoki, Zemel, Babette S., Becker, Diane M., Borecki, Ingrid B., Evans, Michele K., Harris, Tamara B., Hirschhorn, Joel N., Li, Yun, Patel, Sanjay R., Psaty, Bruce M., Rotter, Jerome I., Wilson, James G., Bowden, Donald W., Cupples, L. Adrienne, Haiman, Christopher A., Loos, Ruth J. F., and North, Kari E.

Subjects
Biology and Life Sciences, Computational Biology, Genome Analysis, Genome-Wide Association Studies, Genetics, Genomics, Human Genetics, Mathematical and Statistical Techniques, Statistical Methods, Meta-Analysis, Physical Sciences, Mathematics, Statistics (Mathematics), Genetic Loci, Genomics Statistics, People and Places, Population Groupings, Ethnicities, Africans, Alleles, Trait Locus Analysis, Cell Biology, Signal Transduction, Cell Signaling, Genomic Signal Processing
Abstract

Genome-wide association studies (GWAS) have identified >300 loci associated with measures of adiposity including body mass index (BMI) and waist-to-hip ratio (adjusted for BMI, WHRadjBMI), but few have been identified through screening of the African ancestry genomes. We performed large scale meta-analyses and replications in up to 52,895 individuals for BMI and up to 23,095 individuals for WHRadjBMI from the African Ancestry Anthropometry Genetics Consortium (AAAGC) using 1000 Genomes phase 1 imputed GWAS to improve coverage of both common and low frequency variants in the low linkage disequilibrium African ancestry genomes. In the sex-combined analyses, we identified one novel locus (TCF7L2/HABP2) for WHRadjBMI and eight previously established loci at P < 5×10−8: seven for BMI, and one for WHRadjBMI in African ancestry individuals. An additional novel locus (SPRYD7/DLEU2) was identified for WHRadjBMI when combined with European GWAS. In the sex-stratified analyses, we identified three novel loci for BMI (INTS10/LPL and MLC1 in men, IRX4/IRX2 in women) and four for WHRadjBMI (SSX2IP, CASC8, PDE3B and ZDHHC1/HSD11B2 in women) in individuals of African ancestry or both African and European ancestry. For four of the novel variants, the minor allele frequency was low (<5%). In the trans-ethnic fine mapping of 47 BMI loci and 27 WHRadjBMI loci that were locus-wide significant (P < 0.05 adjusted for effective number of variants per locus) from the African ancestry sex-combined and sex-stratified analyses, 26 BMI loci and 17 WHRadjBMI loci contained ≤ 20 variants in the credible sets that jointly account for 99% posterior probability of driving the associations. The lead variants in 13 of these loci had a high probability of being causal. As compared to our previous HapMap imputed GWAS for BMI and WHRadjBMI including up to 71,412 and 27,350 African ancestry individuals, respectively, our results suggest that 1000 Genomes imputation showed modest improvement in identifying GWAS loci including low frequency variants. Trans-ethnic meta-analyses further improved fine mapping of putative causal variants in loci shared between the African and European ancestry populations.

Published
2017
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16. A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer.

Author

Al Olama AA, Kote-Jarai Z, Berndt SI, Conti DV, Schumacher F, Han Y, Benlloch S, Hazelett DJ, Wang Z, Saunders E, Leongamornlert D, Lindstrom S, Jugurnauth-Little S, Dadaev T, Tymrakiewicz M, Stram DO, Rand K, Wan P, Stram A, Sheng X, Pooler LC, Park K, Xia L, Tyrer J, Kolonel LN, Le Marchand L, Hoover RN, Machiela MJ, Yeager M, Burdette L, Chung CC, Hutchinson A, Yu K, Goh C, Ahmed M, Govindasami K, Guy M, Tammela TL, Auvinen A, Wahlfors T, Schleutker J, Visakorpi T, Leinonen KA, Xu J, Aly M, Donovan J, Travis RC, Key TJ, Siddiq A, Canzian F, Khaw KT, Takahashi A, Kubo M, Pharoah P, Pashayan N, Weischer M, Nordestgaard BG, Nielsen SF, Klarskov P, Røder MA, Iversen P, Thibodeau SN, McDonnell SK, Schaid DJ, Stanford JL, Kolb S, Holt S, Knudsen B, Coll AH, Gapstur SM, Diver WR, Stevens VL, Maier C, Luedeke M, Herkommer K, Rinckleb AE, Strom SS, Pettaway C, Yeboah ED, Tettey Y, Biritwum RB, Adjei AA, Tay E, Truelove A, Niwa S, Chokkalingam AP, Cannon-Albright L, Cybulski C, Wokołorczyk D, Kluźniak W, Park J, Sellers T, Lin HY, Isaacs WB, Partin AW, Brenner H, Dieffenbach AK, Stegmaier C, Chen C, Giovannucci EL, Ma J, Stampfer M, Penney KL, Mucci L, John EM, Ingles SA, Kittles RA, Murphy AB, Pandha H, Michael A, Kierzek AM, Blot W, Signorello LB, Zheng W, Albanes D, Virtamo J, Weinstein S, Nemesure B, Carpten J, Leske C, Wu SY, Hennis A, Kibel AS, Rybicki BA, Neslund-Dudas C, Hsing AW, Chu L, Goodman PJ, Klein EA, Zheng SL, Batra J, Clements J, Spurdle A, Teixeira MR, Paulo P, Maia S, Slavov C, Kaneva R, Mitev V, Witte JS, Casey G, Gillanders EM, Seminara D, Riboli E, Hamdy FC, Coetzee GA, Li Q, Freedman ML, Hunter DJ, Muir K, Gronberg H, Neal DE, Southey M, Giles GG, Severi G, Cook MB, Nakagawa H, Wiklund F, Kraft P, Chanock SJ, Henderson BE, Easton DF, Eeles RA, and Haiman CA

Subjects
Genome-Wide Association Study, Genotype, Humans, Male, Risk Assessment, Risk Factors, Genetic Loci genetics, Genetic Predisposition to Disease genetics, Polymorphism, Single Nucleotide, Prostatic Neoplasms genetics
Abstract

Genome-wide association studies (GWAS) have identified 76 variants associated with prostate cancer risk predominantly in populations of European ancestry. To identify additional susceptibility loci for this common cancer, we conducted a meta-analysis of > 10 million SNPs in 43,303 prostate cancer cases and 43,737 controls from studies in populations of European, African, Japanese and Latino ancestry. Twenty-three new susceptibility loci were identified at association P < 5 × 10(-8); 15 variants were identified among men of European ancestry, 7 were identified in multi-ancestry analyses and 1 was associated with early-onset prostate cancer. These 23 variants, in combination with known prostate cancer risk variants, explain 33% of the familial risk for this disease in European-ancestry populations. These findings provide new regions for investigation into the pathogenesis of prostate cancer and demonstrate the usefulness of combining ancestrally diverse populations to discover risk loci for disease.

Published
2014
Full Text
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