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Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci

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  1. Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson’s disease

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  2. Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer

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  3. Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing

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  4. Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition

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  5. Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes

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  1. Triglycerides as a shared risk factor between dementia and atherosclerotic cardiovascular disease: a study of 125 727 individuals

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  2. Cardiac chamber volumes and left ventricular mass in people living with HIV and matched uninfected controls

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  3. Impact of cardiovascular risk factors and genetics on 10-year absolute risk of dementia: risk charts for targeted prevention

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  4. Elevated plasma YKL-40 and risk of infectious disease: a prospective study of 94665 individuals from the general population

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Genome-wide association studies (GWAS) and fine-mapping efforts to date have identified more than 100 prostate cancer (PrCa)-susceptibility loci. We meta-analyzed genotype data from a custom high-density array of 46,939 PrCa cases and 27,910 controls of European ancestry with previously genotyped data of 32,255 PrCa cases and 33,202 controls of European ancestry. Our analysis identified 62 novel loci associated (P < 5.0 × 10-8) with PrCa and one locus significantly associated with early-onset PrCa (≤55 years). Our findings include missense variants rs1800057 (odds ratio (OR) = 1.16; P = 8.2 × 10-9; G>C, p.Pro1054Arg) in ATM and rs2066827 (OR = 1.06; P = 2.3 × 10-9; T>G, p.Val109Gly) in CDKN1B. The combination of all loci captured 28.4% of the PrCa familial relative risk, and a polygenic risk score conferred an elevated PrCa risk for men in the ninetieth to ninety-ninth percentiles (relative risk = 2.69; 95% confidence interval (CI): 2.55-2.82) and first percentile (relative risk = 5.71; 95% CI: 5.04-6.48) risk stratum compared with the population average. These findings improve risk prediction, enhance fine-mapping, and provide insight into the underlying biology of PrCa 1 .

Original languageEnglish
JournalNature Genetics
Volume50
Pages (from-to)928-36
ISSN1061-4036
DOIs
Publication statusPublished - 11 Jun 2018

ID: 54774876