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

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  1. Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses

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

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

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

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  1. Arterial hypertension and morphologic abnormalities of cardiac chambers: results from the Copenhagen General Population Study

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  2. Inhibition of Cholesteryl Ester Transfer Protein Preserves High-Density Lipoprotein Cholesterol and Improves Survival in Sepsis

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  3. Association of Low Plasma Transthyretin Concentration With Risk of Heart Failure in the General Population

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  4. Vitamin D levels and the risk of prostate cancer and prostate cancer mortality

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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