Schizophrenia and cardiometabolic abnormalities: A Mendelian randomization study.
Schizophrenia and cardiometabolic abnormalities: A Mendelian randomization study.
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DOI：
10.3389/fgene.2023.1150458
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发表时间：
2023
影响因子：
3.7
通讯作者：
Bramon, Elvira
中科院分区：
文献类型：
--
作者：
Khani, Noushin Saadullah;Cotic, Marius;Wang, Baihan;Abidoph, Rosemary;Mills, Georgina;Richards-Belle, Alvin;Perry, Benjamin I. I.;Khandaker, Golam M. M.;Bramon, Elvira
关键词：
背景资料：已知诊断为精神分裂症的个体由于身体健康状况不佳，特别是心血管疾病，糖尿病和肥胖而具有过早死亡的高风险。该患者人群中这些身体健康结果的原因是复杂的。尽管某些抗精神病药物和生活方式因素的心脏代谢不良反应有充分的证据，精神分裂症可能有一个独立的影响。 目的：采用双向双样本孟德尔随机化（MR）分析，研究是否有证据表明精神分裂症与心脏代谢特征（血脂、人体测量特征、血脂特征、血压）存在因果关系，反之亦然。 研究方法：我们在正向分析（精神分裂症与心脏代谢性状）中使用了来自最新精神病基因组学联盟GWAS（n = 130，644）的185个与精神分裂症相关的遗传变异，在反向分析（心脏代谢性状与精神分裂症）中使用了来自不同联盟的与心脏代谢性状相关的遗传变异，两者都具有全基因组显著性（5 × 10−8）。主要的方法是逆方差加权MR，辅助方法，如MR-Egger，以及中位数和基于模式的方法。 结果如下：在前向分析中，精神分裂症与略高的低密度脂蛋白胆固醇水平相关（LDL每对数比值增加精神分裂症风险的0.013 SD变化，95% CI，0.001-0.024 SD; p = 0.027）和总胆固醇水平（精神分裂症风险中每对数比值增加的总胆固醇变化为0.013 SD，95% CI，0.002-0.025 SD; p = 0.023）。然而，这些协会没有生存多次测试校正。在反向分析中，没有证据表明心脏代谢特征对精神分裂症有因果关系。 讨论：精神分裂症患者的血脂异常和肥胖不太可能主要由精神分裂症本身驱动。因此，生活方式，饮食，抗精神病药物副作用，以及代谢功能障碍和精神分裂症的共同机制，如低度全身炎症，可能是精神分裂症患者代谢疾病风险明显增加的可能原因。需要进一步的研究来检验共享免疫机制假说。
Background: Individuals with a diagnosis of schizophrenia are known to be at high risk of premature mortality due to poor physical health, especially cardiovascular disease, diabetes, and obesity. The reasons for these physical health outcomes within this patient population are complex. Despite well-documented cardiometabolic adverse effects of certain antipsychotic drugs and lifestyle factors, schizophrenia may have an independent effect. Aims: To investigate if there is evidence that schizophrenia is causally related to cardiometabolic traits (blood lipids, anthropometric traits, glycaemic traits, blood pressure) and vice versa using bi-directional two-sample Mendelian randomization (MR) analysis. Methods: We used 185 genetic variants associated with schizophrenia from the latest Psychiatric Genomics Consortium GWAS (n = 130,644) in the forward analysis (schizophrenia to cardiometabolic traits) and genetic variants associated with the cardiometabolic traits from various consortia in the reverse analysis (cardiometabolic traits to schizophrenia), both at genome-wide significance (5 × 10−8). The primary method was inverse-variance weighted MR, supported by supplementary methods such as MR-Egger, as well as median and mode-based methods. Results: In the forward analysis, schizophrenia was associated with slightly higher low-density lipoprotein (LDL) cholesterol levels (0.013 SD change in LDL per log odds increase in schizophrenia risk, 95% CI, 0.001–0.024 SD; p = 0.027) and total cholesterol levels (0.013 SD change in total cholesterol per log odds increase in schizophrenia risk, 95% CI, 0.002–0.025 SD; p = 0.023). However, these associations did not survive multiple testing corrections. There was no evidence of a causal effect of cardiometabolic traits on schizophrenia in the reverse analysis. Discussion: Dyslipidemia and obesity in schizophrenia patients are unlikely to be driven primarily by schizophrenia itself. Therefore, lifestyle, diet, antipsychotic drugs side effects, as well as shared mechanisms for metabolic dysfunction and schizophrenia such as low-grade systemic inflammation could be possible reasons for the apparent increased risk of metabolic disease in people with schizophrenia. Further research is needed to examine the shared immune mechanism hypothesis.
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DOI：
10.1016/j.bbi.2021.07.009
发表时间：
2021-10
期刊：
Brain, behavior, and immunity
影响因子：
--
作者：
Perry BI;Upthegrove R;Kappelmann N;Jones PB;Burgess S;Khandaker GM
通讯作者：
Khandaker GM
血糖和胰岛素相关特征、2 型糖尿病和精神分裂症风险：孟德尔随机研究
影响因子：
11.1
作者：
Li Z;Chen P;Chen J;Xu Y;Wang Q;Li X;Li C;He L;Shi Y
通讯作者：
Shi Y
影响因子：
30.8
作者：
Chen J;Spracklen CN;Marenne G;Varshney A;Corbin LJ;Luan J;Willems SM;Wu Y;Zhang X;Horikoshi M;Boutin TS;Mägi R;Waage J;Li-Gao R;Chan KHK;Yao J;Anasanti MD;Chu AY;Claringbould A;Heikkinen J;Hong J;Hottenga JJ;Huo S;Kaakinen MA;Louie T;März W;Moreno-Macias H;Ndungu A;Nelson SC;Nolte IM;North KE;Raulerson CK;Ray D;Rohde R;Rybin D;Schurmann C;Sim X;Southam L;Stewart ID;Wang CA;Wang Y;Wu P;Zhang W;Ahluwalia TS;Appel EVR;Bielak LF;Brody JA;Burtt NP;Cabrera CP;Cade BE;Chai JF;Chai X;Chang LC;Chen CH;Chen BH;Chitrala KN;Chiu YF;de Haan HG;Delgado GE;Demirkan A;Duan Q;Engmann J;Fatumo SA;Gayán J;Giulianini F;Gong JH;Gustafsson S;Hai Y;Hartwig FP;He J;Heianza Y;Huang T;Huerta-Chagoya A;Hwang MY;Jensen RA;Kawaguchi T;Kentistou KA;Kim YJ;Kleber ME;Kooner IK;Lai S;Lange LA;Langefeld CD;Lauzon M;Li M;Ligthart S;Liu J;Loh M;Long J;Lyssenko V;Mangino M;Marzi C;Montasser ME;Nag A;Nakatochi M;Noce D;Noordam R;Pistis G;Preuss M;Raffield L;Rasmussen-Torvik LJ;Rich SS;Robertson NR;Rueedi R;Ryan K;Sanna S;Saxena R;Schraut KE;Sennblad B;Setoh K;Smith AV;Sparsø T;Strawbridge RJ;Takeuchi F;Tan J;Trompet S;van den Akker E;van der Most PJ;Verweij N;Vogel M;Wang H;Wang C;Wang N;Warren HR;Wen W;Wilsgaard T;Wong A;Wood AR;Xie T;Zafarmand MH;Zhao JH;Zhao W;Amin N;Arzumanyan Z;Astrup A;Bakker SJL;Baldassarre D;Beekman M;Bergman RN;Bertoni A;Blüher M;Bonnycastle LL;Bornstein SR;Bowden DW;Cai Q;Campbell A;Campbell H;Chang YC;de Geus EJC;Dehghan A;Du S;Eiriksdottir G;Farmaki AE;Frånberg M;Fuchsberger C;Gao Y;Gjesing AP;Goel A;Han S;Hartman CA;Herder C;Hicks AA;Hsieh CH;Hsueh WA;Ichihara S;Igase M;Ikram MA;Johnson WC;Jørgensen ME;Joshi PK;Kalyani RR;Kandeel FR;Katsuya T;Khor CC;Kiess W;Kolcic I;Kuulasmaa T;Kuusisto J;Läll K;Lam K;Lawlor DA;Lee NR;Lemaitre RN;Li H;Lifelines Cohort Study;Lin SY;Lindström J;Linneberg A;Liu J;Lorenzo C;Matsubara T;Matsuda F;Mingrone G;Mooijaart S;Moon S;Nabika T;Nadkarni GN;Nadler JL;Nelis M;Neville MJ;Norris JM;Ohyagi Y;Peters A;Peyser PA;Polasek O;Qi Q;Raven D;Reilly DF;Reiner A;Rivideneira F;Roll K;Rudan I;Sabanayagam C;Sandow K;Sattar N;Schürmann A;Shi J;Stringham HM;Taylor KD;Teslovich TM;Thuesen B;Timmers PRHJ;Tremoli E;Tsai MY;Uitterlinden A;van Dam RM;van Heemst D;van Hylckama Vlieg A;van Vliet-Ostaptchouk JV;Vangipurapu J;Vestergaard H;Wang T;Willems van Dijk K;Zemunik T;Abecasis GR;Adair LS;Aguilar-Salinas CA;Alarcón-Riquelme ME;An P;Aviles-Santa L;Becker DM;Beilin LJ;Bergmann S;Bisgaard H;Black C;Boehnke M;Boerwinkle E;Böhm BO;Bønnelykke K;Boomsma DI;Bottinger EP;Buchanan TA;Canouil M;Caulfield MJ;Chambers JC;Chasman DI;Chen YI;Cheng CY;Collins FS;Correa A;Cucca F;de Silva HJ;Dedoussis G;Elmståhl S;Evans MK;Ferrannini E;Ferrucci L;Florez JC;Franks PW;Frayling TM;Froguel P;Gigante B;Goodarzi MO;Gordon-Larsen P;Grallert H;Grarup N;Grimsgaard S;Groop L;Gudnason V;Guo X;Hamsten A;Hansen T;Hayward C;Heckbert SR;Horta BL;Huang W;Ingelsson E;James PS;Jarvelin MR;Jonas JB;Jukema JW;Kaleebu P;Kaplan R;Kardia SLR;Kato N;Keinanen-Kiukaanniemi SM;Kim BJ;Kivimaki M;Koistinen HA;Kooner JS;Körner A;Kovacs P;Kuh D;Kumari M;Kutalik Z;Laakso M;Lakka TA;Launer LJ;Leander K;Li H;Lin X;Lind L;Lindgren C;Liu S;Loos RJF;Magnusson PKE;Mahajan A;Metspalu A;Mook-Kanamori DO;Mori TA;Munroe PB;Njølstad I;O'Connell JR;Oldehinkel AJ;Ong KK;Padmanabhan S;Palmer CNA;Palmer ND;Pedersen O;Pennell CE;Porteous DJ;Pramstaller PP;Province MA;Psaty BM;Qi L;Raffel LJ;Rauramaa R;Redline S;Ridker PM;Rosendaal FR;Saaristo TE;Sandhu M;Saramies J;Schneiderman N;Schwarz P;Scott LJ;Selvin E;Sever P;Shu XO;Slagboom PE;Small KS;Smith BH;Snieder H;Sofer T;Sørensen TIA;Spector TD;Stanton A;Steves CJ;Stumvoll M;Sun L;Tabara Y;Tai ES;Timpson NJ;Tönjes A;Tuomilehto J;Tusie T;Uusitupa M;van der Harst P;van Duijn C;Vitart V;Vollenweider P;Vrijkotte TGM;Wagenknecht LE;Walker M;Wang YX;Wareham NJ;Watanabe RM;Watkins H;Wei WB;Wickremasinghe AR;Willemsen G;Wilson JF;Wong TY;Wu JY;Xiang AH;Yanek LR;Yengo L;Yokota M;Zeggini E;Zheng W;Zonderman AB;Rotter JI;Gloyn AL;McCarthy MI;Dupuis J;Meigs JB;Scott RA;Prokopenko I;Leong A;Liu CT;Parker SCJ;Mohlke KL;Langenberg C;Wheeler E;Morris AP;Barroso I;Meta-Analysis of Glucose and Insulin-related Traits Consortium (MAGIC)
通讯作者：
Meta-Analysis of Glucose and Insulin-related Traits Consortium (MAGIC)
影响因子：
25.8
作者：
Perry BI;Stochl J;Upthegrove R;Zammit S;Wareham N;Langenberg C;Winpenny E;Dunger D;Jones PB;Khandaker GM
通讯作者：
Khandaker GM
影响因子：
11.9
作者：
Aoki, Rei;Saito, Takeo;Ninomiya, Kohei;Shimasaki, Ayu;Ashizawa, Takuma;Ito, Kenta;Ikeda, Masashi;Iwata, Nakao
通讯作者：
Iwata, Nakao