Polygenic contributions to performance on the Balloon Analogue Risk Task.
Polygenic contributions to performance on the Balloon Analogue Risk Task.
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对气球模拟风险任务的性能的多基因贡献。
DOI：
10.1038/s41380-023-02123-x
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发表时间：
2023-08
影响因子：
11
通讯作者：
London, E. D.
中科院分区：
文献类型：
--
作者：
Nurmi, E. L.;Laughlin, C. P.;de Wit, H.;Palmer, A. A.;MacKillop, J.;Cannon, T. D.;Bilder, R. M.;Congdon, E.;Sabb, F. W.;Seaman, L. C.;McElroy, J. J.;Libowitz, M. R.;Weafer, J.;Gray, J.;Dean, A. C.;Hellemann, G. S.;London, E. D.
风险决策是一种常见的、可遗传的内在表型，见于许多精神疾病。其潜在的遗传结构还没有完全被探索。我们在两个独立的欧洲血统样本中检查了气球模拟风险任务(BART)中的行为，该任务测试了风险决策。一个样本(n = 1138)包括健康参与者和一些精神疾病患者(53例精神分裂症，42例双相情感障碍，47例多动症)；另一例(n = 911)排除最近治疗各种精神疾病，但不包括多动症。参与者提供DNA并进行BART，通过平均调整的泵进行索引。我们构建了在每个数据集中发现的多基因风险评分(PRS)，并在另一个数据集中进行了重复测试。随后，结合了这两个样本的全基因组巨型分析，测试了基因与英国生物库样本中的冒险自我报告以及精神病学基因组联盟中以冒险为特征的精神表型(ADHD、躁郁症、酒精使用障碍、以前使用大麻)的相关性。一个数据集中BART性能的PR预测了复制样本中的任务性能(r = 0.13，p = 0.000012，p fdr = 0.000052)，倒数分析也是如此(r = 0.09，p = 0.0083，p fdr=0.04)。排除有精神疾病诊断的参与者也产生了类似的结果。MEGA-GWAS在IGSF21附近发现了单个SNP(rs12023073；p = 3.24 × 10−8)，IGSF21是一种参与抑制性脑突触的蛋白质；需要复制样本来验证这一结果。在我们的大规模样本中，自我报告的大麻使用情况的PR(p = 0.00047，pFDR = 0.0053)，而不是自我报告的冒险或精神障碍状态，预测了BART上的行为。这些发现揭示了BART衡量的高风险决策的多基因架构，并突出了其与大麻使用的重叠。
Risky decision-making is a common, heritable endophenotype seen across many psychiatric disorders. Its underlying genetic architecture is incompletely explored. We examined behavior in the Balloon Analogue Risk Task (BART), which tests risky decision-making, in two independent samples of European ancestry. One sample (n = 1138) comprised healthy participants and some psychiatric patients (53 schizophrenia, 42 bipolar disorder, 47 ADHD); the other (n = 911) excluded for recent treatment of various psychiatric disorders but not ADHD. Participants provided DNA and performed the BART, indexed by mean adjusted pumps. We constructed a polygenic risk score (PRS) for discovery in each dataset and tested it in the other as replication. Subsequently, a genome-wide MEGA-analysis, combining both samples, tested genetic correlation with risk-taking self-report in the UK Biobank sample and psychiatric phenotypes characterized by risk-taking (ADHD, Bipolar Disorder, Alcohol Use Disorder, prior cannabis use) in the Psychiatric Genomics Consortium. The PRS for BART performance in one dataset predicted task performance in the replication sample (r = 0.13, p = 0.000012, pFDR = 0.000052), as did the reciprocal analysis (r = 0.09, p = 0.0083, pFDR=0.04). Excluding participants with psychiatric diagnoses produced similar results. The MEGA-GWAS identified a single SNP (rs12023073; p = 3.24 × 10−8) near IGSF21, a protein involved in inhibitory brain synapses; replication samples are needed to validate this result. A PRS for self-reported cannabis use (p = 0.00047, pFDR = 0.0053), but not self-reported risk-taking or psychiatric disorder status, predicted behavior on the BART in our MEGA-GWAS sample. The findings reveal polygenic architecture of risky decision-making as measured by the BART and highlight its overlap with cannabis use.
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DOI：
10.1523/jneurosci.4433-10.2011
发表时间：
2011-02-16
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Carlson BR;Lloyd KE;Kruszewski A;Kim IH;Rodriguiz RM;Heindel C;Faytell M;Dudek SM;Wetsel WC;Soderling SH
通讯作者：
Soderling SH
影响因子：
11.3
作者：
Gray JC;MacKillop J;Weafer J;Hernandez KM;Gao J;Palmer AA;de Wit H
通讯作者：
de Wit H
影响因子：
22.4
作者：
Hutchison, KE;Stallings, M;Bryan, A
通讯作者：
Bryan, A
影响因子：
3.4
作者：
Iancu OD;Colville A;Walter NAR;Darakjian P;Oberbeck DL;Daunais JB;Zheng CL;Searles RP;McWeeney SK;Grant KA;Hitzemann R
通讯作者：
Hitzemann R
影响因子：
16.6
作者：
Davies G;Lam M;Harris SE;Trampush JW;Luciano M;Hill WD;Hagenaars SP;Ritchie SJ;Marioni RE;Fawns-Ritchie C;Liewald DCM;Okely JA;Ahola-Olli AV;Barnes CLK;Bertram L;Bis JC;Burdick KE;Christoforou A;DeRosse P;Djurovic S;Espeseth T;Giakoumaki S;Giddaluru S;Gustavson DE;Hayward C;Hofer E;Ikram MA;Karlsson R;Knowles E;Lahti J;Leber M;Li S;Mather KA;Melle I;Morris D;Oldmeadow C;Palviainen T;Payton A;Pazoki R;Petrovic K;Reynolds CA;Sargurupremraj M;Scholz M;Smith JA;Smith AV;Terzikhan N;Thalamuthu A;Trompet S;van der Lee SJ;Ware EB;Windham BG;Wright MJ;Yang J;Yu J;Ames D;Amin N;Amouyel P;Andreassen OA;Armstrong NJ;Assareh AA;Attia JR;Attix D;Avramopoulos D;Bennett DA;Böhmer AC;Boyle PA;Brodaty H;Campbell H;Cannon TD;Cirulli ET;Congdon E;Conley ED;Corley J;Cox SR;Dale AM;Dehghan A;Dick D;Dickinson D;Eriksson JG;Evangelou E;Faul JD;Ford I;Freimer NA;Gao H;Giegling I;Gillespie NA;Gordon SD;Gottesman RF;Griswold ME;Gudnason V;Harris TB;Hartmann AM;Hatzimanolis A;Heiss G;Holliday EG;Joshi PK;Kähönen M;Kardia SLR;Karlsson I;Kleineidam L;Knopman DS;Kochan NA;Konte B;Kwok JB;Le Hellard S;Lee T;Lehtimäki T;Li SC;Lill CM;Liu T;Koini M;London E;Longstreth WT Jr;Lopez OL;Loukola A;Luck T;Lundervold AJ;Lundquist A;Lyytikäinen LP;Martin NG;Montgomery GW;Murray AD;Need AC;Noordam R;Nyberg L;Ollier W;Papenberg G;Pattie A;Polasek O;Poldrack RA;Psaty BM;Reppermund S;Riedel-Heller SG;Rose RJ;Rotter JI;Roussos P;Rovio SP;Saba Y;Sabb FW;Sachdev PS;Satizabal CL;Schmid M;Scott RJ;Scult MA;Simino J;Slagboom PE;Smyrnis N;Soumaré A;Stefanis NC;Stott DJ;Straub RE;Sundet K;Taylor AM;Taylor KD;Tzoulaki I;Tzourio C;Uitterlinden A;Vitart V;Voineskos AN;Kaprio J;Wagner M;Wagner H;Weinhold L;Wen KH;Widen E;Yang Q;Zhao W;Adams HHH;Arking DE;Bilder RM;Bitsios P;Boerwinkle E;Chiba-Falek O;Corvin A;De Jager PL;Debette S;Donohoe G;Elliott P;Fitzpatrick AL;Gill M;Glahn DC;Hägg S;Hansell NK;Hariri AR;Ikram MK;Jukema JW;Vuoksimaa E;Keller MC;Kremen WS;Launer L;Lindenberger U;Palotie A;Pedersen NL;Pendleton N;Porteous DJ;Räikkönen K;Raitakari OT;Ramirez A;Reinvang I;Rudan I;Dan Rujescu;Schmidt R;Schmidt H;Schofield PW;Schofield PR;Starr JM;Steen VM;Trollor JN;Turner ST;Van Duijn CM;Villringer A;Weinberger DR;Weir DR;Wilson JF;Malhotra A;McIntosh AM;Gale CR;Seshadri S;Mosley TH Jr;Bressler J;Lencz T;Deary IJ
通讯作者：
Deary IJ