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000179931 041__ $$aEnglish
000179931 082__ $$a610
000179931 1001_ $$aHuan, Tianxiao$$b0
000179931 245__ $$aIntegrative analysis of clinical and epigenetic biomarkers of mortality.
000179931 260__ $$aOxford [u.a.]$$bWiley-Blackwell$$c2022
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000179931 500__ $$a 2022 Jun;21(6):e13608
000179931 520__ $$aDNA methylation (DNAm) has been reported to be associated with many diseases and with mortality. We hypothesized that the integration of DNAm with clinical risk factors would improve mortality prediction. We performed an epigenome-wide association study of whole blood DNAm in relation to mortality in 15 cohorts (n = 15,013). During a mean follow-up of 10 years, there were 4314 deaths from all causes including 1235 cardiovascular disease (CVD) deaths and 868 cancer deaths. Ancestry-stratified meta-analysis of all-cause mortality identified 163 CpGs in European ancestry (EA) and 17 in African ancestry (AA) participants at p < 1 × 10-7 , of which 41 (EA) and 16 (AA) were also associated with CVD death, and 15 (EA) and 9 (AA) with cancer death. We built DNAm-based prediction models for all-cause mortality that predicted mortality risk after adjusting for clinical risk factors. The mortality prediction model trained by integrating DNAm with clinical risk factors showed an improvement in prediction of cancer death with 5% increase in the C-index in a replication cohort, compared with the model including clinical risk factors alone. Mendelian randomization identified 15 putatively causal CpGs in relation to longevity, CVD, or cancer risk. For example, cg06885782 (in KCNQ4) was positively associated with risk for prostate cancer (Beta = 1.2, PMR = 4.1 × 10-4 ) and negatively associated with longevity (Beta = -1.9, PMR = 0.02). Pathway analysis revealed that genes associated with mortality-related CpGs are enriched for immune- and cancer-related pathways. We identified replicable DNAm signatures of mortality and demonstrated the potential utility of CpGs as informative biomarkers for prediction of mortality risk.
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000179931 650_7 $$2Other$$aDNA methylation
000179931 650_7 $$2Other$$acancer
000179931 650_7 $$2Other$$acardiovascular disease
000179931 650_7 $$2Other$$amachine learning
000179931 650_7 $$2Other$$amortality
000179931 7001_ $$aNguyen, Steve$$b1
000179931 7001_ $$aColicino, Elena$$b2
000179931 7001_ $$aOchoa-Rosales, Carolina$$b3
000179931 7001_ $$aHill, W David$$b4
000179931 7001_ $$aBrody, Jennifer A$$b5
000179931 7001_ $$aSoerensen, Mette$$b6
000179931 7001_ $$0P:(DE-He78)d19149dd97b17ce55e70abd2f9e64d3d$$aZhang, Yan$$b7
000179931 7001_ $$aBaldassari, Antoine$$b8
000179931 7001_ $$aElhadad, Mohamed Ahmed$$b9
000179931 7001_ $$aToshiko, Tanaka$$b10
000179931 7001_ $$aZheng, Yinan$$b11
000179931 7001_ $$aDomingo-Relloso, Arce$$b12
000179931 7001_ $$aLee, Dong Heon$$b13
000179931 7001_ $$aMa, Jiantao$$b14
000179931 7001_ $$aYao, Chen$$b15
000179931 7001_ $$aLiu, Chunyu$$b16
000179931 7001_ $$aHwang, Shih-Jen$$b17
000179931 7001_ $$aJoehanes, Roby$$b18
000179931 7001_ $$aFornage, Myriam$$b19
000179931 7001_ $$aBressler, Jan$$b20
000179931 7001_ $$avan Meurs, Joyce B J$$b21
000179931 7001_ $$aDebrabant, Birgit$$b22
000179931 7001_ $$aMengel-From, Jonas$$b23
000179931 7001_ $$aHjelmborg, Jacob$$b24
000179931 7001_ $$aChristensen, Kaare$$b25
000179931 7001_ $$aVokonas, Pantel$$b26
000179931 7001_ $$aSchwartz, Joel$$b27
000179931 7001_ $$aGahrib, Sina A$$b28
000179931 7001_ $$aSotoodehnia, Nona$$b29
000179931 7001_ $$aSitlani, Colleen M$$b30
000179931 7001_ $$aKunze, Sonja$$b31
000179931 7001_ $$aGieger, Christian$$b32
000179931 7001_ $$aPeters, Annette$$b33
000179931 7001_ $$aWaldenberger, Melanie$$b34
000179931 7001_ $$aDeary, Ian J$$b35
000179931 7001_ $$aFerrucci, Luigi$$b36
000179931 7001_ $$aQu, Yishu$$b37
000179931 7001_ $$aGreenland, Philip$$b38
000179931 7001_ $$aLloyd-Jones, Donald M$$b39
000179931 7001_ $$aHou, Lifang$$b40
000179931 7001_ $$aBandinelli, Stefania$$b41
000179931 7001_ $$aVoortman, Trudy$$b42
000179931 7001_ $$aHermann, Brenner$$b43
000179931 7001_ $$aBaccarelli, Andrea$$b44
000179931 7001_ $$aWhitsel, Eric$$b45
000179931 7001_ $$aPankow, James S$$b46
000179931 7001_ $$00000-0003-1843-8724$$aLevy, Daniel$$b47
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