Association of Polygenic Risk for Attention-Deficit/Hyperactivity Disorder With Co-occurring Traits and Disorders.
Association of Polygenic Risk for Attention-Deficit/Hyperactivity Disorder With Co-occurring Traits and Disorders.
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DOI：
10.1016/j.bpsc.2017.11.013
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发表时间：
2018-07
期刊：
影响因子：
--
通讯作者：
Kuntsi J
中科院分区：
文献类型：
--
作者：
Du Rietz E;Coleman J;Glanville K;Choi SW;O'Reilly PF;Kuntsi J
最近的一项大规模全基因组关联研究首次确定了12个基因座的遗传变异与注意力缺陷/多动障碍（ADHD）显著相关。在这项研究中，我们使用了一个强大的多基因的方法，多基因得分来自全基因组关联研究，调查ADHD和经常共同发生的性状和疾病之间的病因重叠。来自大基因组关联研究（20，183例病例和35，191例对照受试者）的ADHD多基因风险评分在英国生物银行招募的大规模成人人群样本（N = 135，726）中计算。进行回归分析以调查ADHD的多基因风险是否与该人群样本中的相关性状和障碍相关。通过在模型中纳入相互作用项，研究了性别的影响。ADHD的多基因风险显著正向预测体重指数（R2 = 0.45%; p = 5 × 10 − 129），神经质（R2 = 0.09%; p = 2 × 10 − 24），抑郁（R2 = 0.11%; p = 2 × 10 − 13），焦虑（R2 = 0.06%; p = 3 × 10 − 4），冒险（R2 = 0.12%; p = 9 × 10 − 25），酒精摄入量（R2 = 0.09%; p = 8 × 10 − 29）、吸烟（R2 = 0.33%; p = 4 × 10 − 21）、酒精依赖（R2 = 0.21%; p = 5 × 10 − 6）和负面预测的语言-数字推理（R2 = 0.38%; p = 5 × 10 − 36）。多基因风险评分并不能显著预测精神分裂症或双相情感障碍，尽管这可能是因为诊断病例数量较少。我们发现多动症的多基因风险和性别对任何表型都没有相互作用。我们的研究结果表明，临床诊断的ADHD风险的常见遗传变异也有助于提高身体质量指数，神经质，焦虑和抑郁症，酒精和尼古丁的使用，冒险以及一般人群的一般认知能力较低。这些发现表明，ADHD的几个特征的共同出现部分是由相同的常见遗传变异解释的。
A recent large-scale mega genome-wide association study identified, for the first time, genetic variants at 12 loci significantly associated with attention-deficit/hyperactivity disorder (ADHD). In this study we use a powerful polygenic approach, with polygenic scores derived from the genome-wide association study, to investigate the etiological overlap between ADHD and frequently co-occurring traits and disorders. Polygenic risk scores for ADHD derived from the mega genome-wide association study (20,183 cases and 35,191 control subjects) were computed in a large-scale adult population sample (N = 135,726) recruited by the UK Biobank. Regression analyses were conducted to investigate whether polygenic risk for ADHD is associated with related traits and disorders in this population sample. The effects of sex were investigated via inclusion of an interaction term in the models. Polygenic risk for ADHD significantly and positively predicted body mass index (R2 = .45%; p = 5 × 10−129), neuroticism (R2 = .09%; p = 2 × 10−24), depression (R2 = .11%; p = 2 × 10−13), anxiety (R2 = .06%; p = 3 × 10−4), risk taking (R2 = .12%; p = 9 × 10−25), alcohol intake (R2 = .09%; p = 8 × 10−29), smoking (R2 = .33%; p = 4 × 10−21), alcohol dependency (R2 = .21%; p = 5 × 10−6), and negatively predicted verbal-numerical reasoning (R2 = .38%; p = 5 × 10−36). Polygenic risk scores did not significantly predict schizophrenia or bipolar disorder, although this may be because of the small number of diagnostic cases. We found no interaction effects between polygenic risk for ADHD and sex on any phenotypes. Our findings suggest that common genetic variation underlying risk for clinically diagnosed ADHD also contributes to higher body mass index, neuroticism, anxiety and depressive disorders, alcohol and nicotine use, risk taking, and lower general cognitive ability in the general population. These findings suggest that the co-occurrence of several traits with ADHD is partly explained by the same common genetic variants.
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DOI：
10.1093/bioinformatics/btu848
发表时间：
2015-05-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Euesden J;Lewis CM;O'Reilly PF
通讯作者：
O'Reilly PF
影响因子：
11
作者：
Davies G;Marioni RE;Liewald DC;Hill WD;Hagenaars SP;Harris SE;Ritchie SJ;Luciano M;Fawns-Ritchie C;Lyall D;Cullen B;Cox SR;Hayward C;Porteous DJ;Evans J;McIntosh AM;Gallacher J;Craddock N;Pell JP;Smith DJ;Gale CR;Deary IJ
通讯作者：
Deary IJ
DOI：
10.1176/appi.ajp.2013.12081129
发表时间：
2013-08
期刊：
The American journal of psychiatry
影响因子：
--
作者：
Hamshere ML;Langley K;Martin J;Agha SS;Stergiakouli E;Anney RJ;Buitelaar J;Faraone SV;Lesch KP;Neale BM;Franke B;Sonuga-Barke E;Asherson P;Merwood A;Kuntsi J;Medland SE;Ripke S;Steinhausen HC;Freitag C;Reif A;Renner TJ;Romanos M;Romanos J;Warnke A;Meyer J;Palmason H;Vasquez AA;Lambregts-Rommelse N;Roeyers H;Biederman J;Doyle AE;Hakonarson H;Rothenberger A;Banaschewski T;Oades RD;McGough JJ;Kent L;Williams N;Owen MJ;Holmans P;O'Donovan MC;Thapar A
通讯作者：
Thapar A
影响因子：
10.5
作者：
Larsson, Henrik;Ryden, Eleonore;Landen, Mikael
通讯作者：
Landen, Mikael
影响因子：
30.8
作者：
Lee, S. Hong;Ripke, Stephan;Neale, Benjamin M.;Faraone, Stephen V.;Purcell, Shaun M.;Perlis, Roy H.;Mowry, Bryan J.;Thapar, Anita;Goddard, Michael E.;Witte, John S.;Absher, Devin;Agartz, Ingrid;Akil, Huda;Amin, Farooq;Andreassen, Ole A.;Anjorin, Adebayo;Anney, Richard;Anttila, Verneri;Arking, Dan E.;Asherson, Philip;Azevedo, Maria H.;Backlund, Lena;Badner, Judith A.;Bailey, Anthony J.;Banaschewski, Tobias;Barchas, Jack D.;Barnes, Michael R.;Barrett, Thomas B.;Bass, Nicholas;Battaglia, Agatino;Bauer, Michael;Bayes, Monica;Bellivier, Frank;Bergen, Sarah E.;Berrettini, Wade;Betancur, Catalina;Bettecken, Thomas;Biederman, Joseph;Binder, Elisabeth B.;Black, Donald W.;Blackwood, Douglas H. R.;Bloss, Cinnamon S.;Boehnke, Michael;Boomsma, Dorret I.;Breen, Gerome;Breuer, Rene;Bruggeman, Richard;Cormican, Paul;Buccola, Nancy G.;Buitelaar, Jan K.;Bunney, William E.;Buxbaum, Joseph D.;Byerley, William F.;Byrne, Enda M.;Caesar, Sian;Cahn, Wiepke;Cantor, Rita M.;Casas, Miguel;Chakravarti, Aravinda;Chambert, Kimberly;Choudhury, Khalid;Cichon, Sven;Cloninger, C. Robert;Collier, David A.;Cook, Edwin H.;Coon, Hilary;Cormand, Bru;Corvin, Aiden;Coryell, William H.;Craig, David W.;Craig, Ian W.;Crosbie, Jennifer;Cuccaro, Michael L.;Curtis, David;Czamara, Darina;Datta, Susmita;Dawson, Geraldine;Day, Richard;De Geus, Eco J.;Degenhardt, Franziska;Djurovic, Srdjan;Donohoe, Gary J.;Doyle, Alysa E.;Duan, Jubao;Dudbridge, Frank;Duketis, Eftichia;Ebstein, Richard P.;Edenberg, Howard J.;Elia, Josephine;Ennis, Sean;Etain, Bruno;Fanous, Ayman;Farmer, Anne E.;Ferrier, I. 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F.;Maestrini, Elena;Magnusson, Patrik K. E.;Mahon, Pamela B.;Maier, Wolfgang;Malhotra, Anil K.;Mane, Shrikant M.;Martin, Christa L.;Martin, Nicholas G.;Mattheisen, Manuel;Matthews, Keith;Mattingsdal, Morten;McCarroll, Steven A.;McGhee, Kevin A.;McGough, James J.;McGrath, Patrick J.;McGuffin, Peter;McInnis, Melvin G.;McIntosh, Andrew;McKinney, Rebecca;McLean, Alan W.;McMahon, Francis J.;McMahon, William M.;McQuillin, Andrew;Medeiros, Helena;Medland, Sarah E.;Meier, Sandra;Melle, Ingrid;Meng, Fan;Meyer, Jobst;Middeldorp, Christel M.;Middleton, Lefkos;Milanova, Vihra;Miranda, Ana;Monaco, Anthony P.;Montgomery, Grant W.;Moran, Jennifer L.;Moreno-De-Luca, Daniel;Morken, Gunnar;Morris, Derek W.;Morrow, Eric M.;Moskvina, Valentina;Muglia, Pierandrea;Muehleisen, Thomas W.;Muir, Walter J.;Mueller-Myhsok, Bertram;Murtha, Michael;Myers, Richard M.;Myin-Germeys, Inez;Neale, Michael C.;Nelson, Stan F.;Nievergelt, Caroline M.;Nikolov, Ivan;Nimgaonkar, Vishwajit;Nolen, Willem A.;Noethen, Markus M.;Nurnberger, John I.;Nwulia, Evaristus A.;Nyholt, Dale R.;O'Dushlaine, Colm;Oades, Robert D.;Olincy, Ann;Oliveira, Guiomar;Olsen, Line;Ophoff, Roel A.;Osby, Urban;Owen, Michael J.;Palotie, Aarno;Parr, Jeremy R.;Paterson, Andrew D.;Pato, Carlos N.;Pato, Michele T.;Penninx, Brenda W.;Pergadia, Michele L.;Pericak-Vance, Margaret A.;Pickard, Benjamin S.;Pimm, Jonathan;Piven, Joseph;Posthuma, Danielle;Potash, James B.;Poustka, Fritz;Propping, Peter;Puri, Vinay;Quested, Digby J.;Quinn, Emma M.;Antoni Ramos-Quiroga, Josep;Rasmussen, Henrik B.;Raychaudhuri, Soumya;Rehnstroem, Karola;Reif, Andreas;Ribases, Marta;Rice, John P.;Rietschel, Marcella;Roeder, Kathryn;Roeyers, Herbert;Rossin, Lizzy;Rothenberger, Aribert;Rouleau, Guy;Ruderfer, Douglas;Rujescu, Dan;Sanders, Alan R.;Sanders, Stephan J.;Santangelo, Susan L.;Sergeant, Joseph A.;Schachar, Russell;Schalling, Martin;Schatzberg, Alan F.;Scheftner, William A.;Schellenberg, Gerard D.;Scherer, Stephen W.;Schork, Nicholas J.;Schulze, Thomas G.;Schumacher, Johannes;Schwarz, Markus;Scolnick, Edward;Scott, Laura J.;Shi, Jianxin;Shilling, Paul D.;Shyn, Stanley I.;Silverman, Jeremy M.;Slager, Susan L.;Smalley, Susan L.;Smit, Johannes H.;Smith, Erin N.;Sonuga-Barke, Edmund J. 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通讯作者：
Wray, Naomi R.