Han, YingHazelett, DennisWiklund, FredrikSchumacher, FredrickStram, DanielBerndt, SonjaWang, ZhaomingRand, KristinHoover, RobertMachiela, MitchellYeager, MeridethBurdette, LaurieChung, CharlesHutchinson, AmyYu, KaiXu, JianfengTravis, RuthKey, TimothySiddiq, AfshanCanzian, FedericoTakahashi, AtsushiKubo, MichiakiStanford, JanetKolb, SuzanneGapstur, SusanDiver, W. RyanStevens, VictoriaStrom, SaraPettaway, CurtisOlama, Ali Amin AlKote-Jarai, ZsofiaEeles, RosalindYeboah, EdwardTettey, YaoBiritwum, RichardAdjei, AndrewTay, EvelynTruelove, AnnNiwa, ShelleyChokkalingam, AnandIsaacs, WilliamChen, ConstanceLindstrom, SaraLe Marchand, LoicGiovannucci, EdwardPomerantz, MarkLong, HenryLi, FugenMa, JingStampfer, MeirJohn, EstherIngles, SueKittles, RickMurphy, AdamBlot, WilliamSignorello, LisaZheng, WeiAlbanes, DemetriusVirtamo, JarmoWeinstein, StephanieNemesure, BarbaraCarpten, JohnLeske, M. CristinaWu, Suh-YuhHennis, AnselmRybicki, BenjaminNeslund-Dudas, ChristineHsing, AnnChu, LisaGoodman, PhyllisKlein, EricZheng, S. LillyWitte, JohnCasey, GrahamRiboli, ElioLi, QiyuanFreedman, MatthewHunter, DavidGronberg, HenrikCook, MichaelNakagawa, HidewakiKraft, PeterChanock, StephenEaston, DouglasHenderson, BrianCoetzee, GerhardConti, DavidHaiman, Christopher2019-09-052015Han, Ying, Dennis J. Hazelett, Fredrik Wiklund, Fredrick R. Schumacher, Daniel O. Stram, Sonja I. Berndt, Zhaoming Wang, et al. 2015. “Integration of Multiethnic Fine-Mapping and Genomic Annotation to Prioritize Candidate Functional SNPs at Prostate Cancer Susceptibility Regions.” Human Molecular Genetics 24 (19): 5603–18. https://doi.org/10.1093/hmg/ddv269.0964-69061460-2083http://nrs.harvard.edu/urn-3:HUL.InstRepos:41292523Interpretation of biological mechanisms underlying genetic risk associations for prostate cancer is complicated by the relatively large number of risk variants (n = 100) and the thousands of surrogate SNPs in linkage disequilibrium. Here, we combined three distinct approaches: multiethnic fine-mapping, putative functional annotation (based upon epigenetic data and genome-encoded features), and expression quantitative trait loci (eQTL) analyses, in an attempt to reduce this complexity. We examined 67 risk regions using genotyping and imputation-based fine-mapping in populations of European (cases/controls: 8600/6946), African (cases/controls: 5327/5136), Japanese (cases/controls: 2563/4391) and Latino (cases/controls: 1034/1046) ancestry. Markers at 55 regions passed a region-specific significance threshold (P-value cutoff range: 3.9 x 10(-4)-5.6 x 10(-3)) and in 30 regions we identified markers that were more significantly associated with risk than the previously reported variants in the multiethnic sample. Novel secondary signals (P < 5.0 x 10(-6)) were also detected in two regions (rs13062436/3q21 and rs17181170/3p12). Among 666 variants in the 55 regions with P-values within one order of magnitude of the most-associated marker, 193 variants (29%) in 48 regions overlapped with epigenetic or other putative functional marks. In 11 of the 55 regions, cis-eQTLs were detected with nearby genes. For 12 of the 55 regions (22%), the most significant region-specific, prostate-cancer associated variant represented the strongest candidate functional variant based on our annotations; the number of regions increased to 20 (36%) and 27 (49%) when examining the 2 and 3 most significantly associated variants in each region, respectively. These results have prioritized subsets of candidate variants for downstream functional evaluation.en-USJournal Article2019-09-0510.1093/hmg/ddv269