Predicting Complex Traits and Exposures From Polygenic Scores and Blood and Buccal DNA Methylation Profiles.
Predicting Complex Traits and Exposures From Polygenic Scores and Blood and Buccal DNA Methylation Profiles.
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DOI：
10.3389/fpsyt.2021.688464
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发表时间：
2021
影响因子：
4.7
通讯作者：
van Dongen J
中科院分区：
文献类型：
--
作者：
Odintsova VV;Rebattu V;Hagenbeek FA;Pool R;Beck JJ;Ehli EA;van Beijsterveldt CEM;Ligthart L;Willemsen G;de Geus EJC;Hottenga JJ;Boomsma DI;van Dongen J
我们研究了甲基化评分（MS）和多基因评分（PGS）在出生体重、BMI、产前母亲吸烟暴露和吸烟状况方面的表现，以评估MS在多组学预测模型中对这些特征和超过PGS的暴露的预测程度。MS可能被视为PGS的表观遗传等同物，但由于其动态性质和非遗传暴露的敏感性，可能会增加独立于PGS的复杂性状预测。MS和PGS是根据来自荷兰双胞胎登记中心的成人血样（Illumina 450k, N = 2431，平均年龄35.6）和儿童口腔样本（Illumina EPIC, N = 1128，平均年龄9.6）的基因型数据和dna甲基化数据计算的。构建评分的权重来自基于全血或脐带血甲基化数据和全基因组关联研究（GWASs）的大型表观基因组关联研究（EWASs）的结果。在成人中，血液中的MSs独立于pgs预测，并且在BMI，产前母亲吸烟和吸烟状况方面优于pgs，但在出生体重方面没有。多组学预测模型解释的最大方差是目前吸烟和从不吸烟（54.6%），其中54.4%被MS捕获。两个预测因子捕获了16%的戒烟和从不吸烟的开始方差（MS:15.5%, PGS: 0.5%）， 17.7%的产前母亲吸烟方差（MS:16.9%, PGS: 0.8%）， 11.9%的BMI方差（MS: 6.4%, PGS 5.5%）和1.9%的出生体重方差（MS: 0.4%, PGS: 1.5%）。在儿童中，口腔样本中的MSs没有显示出独立的预测价值。这两个预测因子解释的最大方差是产前母亲吸烟（2.6%），其中MSs贡献了1.5%。这些结果表明，成年人的血液DNA MS可以解释当前吸烟、曾经吸烟、产前吸烟和BMI之间的巨大差异，但不能解释出生体重。颊细胞DNA甲基化评分具有较低的预测价值，这可能是由于EWAS发现研究中的组织和目标样本不同，以及年龄不同。该研究说明了将多基因评分与甲基化数据信息结合起来用于复杂性状和暴露预测的价值。
We examined the performance of methylation scores (MS) and polygenic scores (PGS) for birth weight, BMI, prenatal maternal smoking exposure, and smoking status to assess the extent to which MS could predict these traits and exposures over and above the PGS in a multi-omics prediction model. MS may be seen as the epigenetic equivalent of PGS, but because of their dynamic nature and sensitivity of non-genetic exposures may add to complex trait prediction independently of PGS. MS and PGS were calculated based on genotype data and DNA-methylation data in blood samples from adults (Illumina 450 K; N = 2,431; mean age 35.6) and in buccal samples from children (Illumina EPIC; N = 1,128; mean age 9.6) from the Netherlands Twin Register. Weights to construct the scores were obtained from results of large epigenome-wide association studies (EWASs) based on whole blood or cord blood methylation data and genome-wide association studies (GWASs). In adults, MSs in blood predicted independently from PGSs, and outperformed PGSs for BMI, prenatal maternal smoking, and smoking status, but not for birth weight. The largest amount of variance explained by the multi-omics prediction model was for current vs. never smoking (54.6%) of which 54.4% was captured by the MS. The two predictors captured 16% of former vs. never smoking initiation variance (MS:15.5%, PGS: 0.5%), 17.7% of prenatal maternal smoking variance (MS:16.9%, PGS: 0.8%), 11.9% of BMI variance (MS: 6.4%, PGS 5.5%), and 1.9% of birth weight variance (MS: 0.4%, PGS: 1.5%). In children, MSs in buccal samples did not show independent predictive value. The largest amount of variance explained by the two predictors was for prenatal maternal smoking (2.6%), where the MSs contributed 1.5%. These results demonstrate that blood DNA MS in adults explain substantial variance in current smoking, large variance in former smoking, prenatal smoking, and BMI, but not in birth weight. Buccal cell DNA methylation scores have lower predictive value, which could be due to different tissues in the EWAS discovery studies and target sample, as well as to different ages. This study illustrates the value of combining polygenic scores with information from methylation data for complex traits and exposure prediction.
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影响因子：
64.8
作者：
Horikoshi, Momoko;Beaumont, Robin N.;Day, Felix R.;Warrington, Nicole M.;Kooijman, Marjolein N.;Fernandez-Tajes, Juan;Feenstra, Bjarke;van Zuydam, Natalie R.;Gaulton, Kyle J.;Grarup, Niels;Bradfield, Jonathan P.;Strachan, David P.;Li-Gao, Ruifang;Ahluwalia, Tarunveer S.;Kreiner, Eskil;Rueedi, Rico;Lyytikainen, Leo-Pekka;Cousminer, Diana L.;Wu, Ying;Thiering, Elisabeth;Wang, Carol A.;Have, Christian T.;Hottenga, Jouke-Jan;Vilor-Tejedor, Natalia;Joshi, Peter K.;Boh, Eileen Tai Hui;Ntalla, Ioanna;Pitkanen, Niina;Mahajan, Anubha;van Leeuwen, Elisabeth M.;Joro, Raimo;Lagou, Vasiliki;Nodzenski, Michael;Diver, Louise A.;Zondervan, Krina T.;Bustamante, Mariona;Marques-Vidal, Pedro;Mercader, Josep M.;Bennett, Amanda J.;Rahmioglu, Nilufer;Nyholt, Dale R.;Ma, Ronald C. W.;Tam, Claudia H. T.;Tam, Wing Hung;Ganesh, Santhi K.;van Rooij, Frank J. A.;Jones, Samuel E.;Loh, Po-Ru;Ruth, Katherine S.;Tuke, Marcus A.;Tyrrell, Jessica;Wood, Andrew R.;Yaghootkar, Hanieh;Scholtens, Denise M.;Paternoster, Lavinia;Prokopenko, Inga;Kovacs, Peter;Atalay, Mustafa;Willems, Sara M.;Panoutsopoulou, Kalliope;Wang, Xu;Carstensen, Lisbeth;Geller, Frank;Schraut, Katharina E.;Murcia, Mario;van Beijsterveldt, Catharina E. M.;Willemsen, Gonneke;Appel, Emil V. R.;Fonvig, Cilius E.;Trier, Caecilie;Tiesler, Carla M. T.;Standl, Marie;Kutalik, Zoltan;Bonas-Guarch, Silvia;Hougaard, David M.;Sanchez, Friman;Torrents, David;Waage, Johannes;Hollegaard, Mads V.;de Haan, Hugoline G.;Rosendaal, Frits R.;Medina-Gomez, Carolina;Ring, Susan M.;Hemani, Gibran;McMahon, George;Robertson, Neil R.;Groves, Christopher J.;Langenberg, Claudia;Luan, Jian'an;Scott, Robert A.;Zhao, Jing Hua;Mentch, Frank D.;MacKenzie, Scott M.;Reynolds, Rebecca M.;Lowe, William L.;Toenjes, Anke;Stumvoll, Michael;Lindi, Virpi;Lakka, Timo A.;van Duijn, Cornelia M.;Kiess, Wieland;Koerner, Antje;Sorensen, Thorkild I. A.;Niinikoski, Harri;Pahkala, Katja;Raitakari, Olli T.;Zeggini, Eleftheria;Dedoussis, George V.;Teo, Yik-Ying;Saw, Seang-Mei;Melbye, Mads;Campbell, Harry;Wilson, James F.;Vrijheid, Martine;de Geus, Eco J. C. N.;Boomsma, Dorret I.;Kadarmideen, Haja N.;Holm, Jens-Christian;Hansen, Torben;Sebert, Sylvain;Hattersley, Andrew T.;Beilin, Lawrence J.;Newnham, John P.;Pennell, Craig E.;Heinrich, Joachim;Adair, Linda S.;Borja, Judith B.;Mohlke, Karen L.;Eriksson, Johan G.;Widen, Elisabeth;Kahonen, Mika;Viikari, Jorma S.;Lehtimaki, Terho;Vollenweider, Peter;Bonnelykke, Klaus;Bisgaard, Hans;Mook-Kanamori, Dennis O.;Hofman, Albert;Rivadeneira, Fernando;Uitterlinden, Andre G.;Pisinger, Charlotta;Pedersen, Oluf;Power, Christine;Hyppoenen, Elina;Wareham, Nicholas J.;Hakonarson, Hakon;Davies, Eleanor;Walker, Brian R.;Jaddoe, Vincent W. V.;Jaervelin, Marjo-Riitta;Grant, Struan F. A.;Vaag, Allan A.;Lawlor, Debbie A.;Frayling, Timothy M.;Smith, George Davey;Morris, Andrew P.;Ong, Ken K.;Felix, Janine F.;Timpson, Nicholas J.;Perry, John R. B.;Evans, David M.;McCarthy, Mark I.;Freathy, Rachel M.
通讯作者：
Freathy, Rachel M.
影响因子：
3.5
作者：
Beck JJ;Pool R;van de Weijer M;Chen X;Krapohl E;Gordon SD;Nygaard M;Debrabant B;Palviainen T;van der Zee MD;Baselmans B;Finnicum CT;Yi L;Lundström S;van Beijsterveldt T;Christiansen L;Heikkilä K;Kittelsrud J;Loukola A;Ollikainen M;Christensen K;Martin NG;Plomin R;Nivard M;Bartels M;Dolan C;Willemsen G;de Geus E;Almqvist C;Magnusson PKE;Mbarek H;Ehli EA;Boomsma DI;Hottenga JJ
通讯作者：
Hottenga JJ
影响因子：
30.8
作者：
Finucane HK;Bulik-Sullivan B;Gusev A;Trynka G;Reshef Y;Loh PR;Anttila V;Xu H;Zang C;Farh K;Ripke S;Day FR;ReproGen Consortium;Schizophrenia Working Group of the Psychiatric Genomics Consortium;RACI Consortium;Purcell S;Stahl E;Lindstrom S;Perry JR;Okada Y;Raychaudhuri S;Daly MJ;Patterson N;Neale BM;Price AL
通讯作者：
Price AL
影响因子：
6.4
作者：
Bartels M;Hendriks A;Mauri M;Krapohl E;Whipp A;Bolhuis K;Conde LC;Luningham J;Fung Ip H;Hagenbeek F;Roetman P;Gatej R;Lamers A;Nivard M;van Dongen J;Lu Y;Middeldorp C;van Beijsterveldt T;Vermeiren R;Hankemeijer T;Kluft C;Medland S;Lundström S;Rose R;Pulkkinen L;Vuoksimaa E;Korhonen T;Martin NG;Lubke G;Finkenauer C;Fanos V;Tiemeier H;Lichtenstein P;Plomin R;Kaprio J;Boomsma DI
通讯作者：
Boomsma DI
影响因子：
9.8
作者：
Joubert, Bonnie R.;Felix, Janine F.;London, Stephanie J.
通讯作者：
London, Stephanie J.