Causal associations between modifiable risk factors and pancreatitis: A comprehensive Mendelian randomization study.
Causal associations between modifiable risk factors and pancreatitis: A comprehensive Mendelian randomization study.
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可改变的危险因素与胰腺炎之间的因果关系：一项全面的孟德尔随机化研究。
DOI：
10.3389/fimmu.2023.1091780
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发表时间：
2023
影响因子：
7.3
通讯作者：
Liao, Zhuan
中科院分区：
文献类型：
--
作者：
Mao, Xiaotong;Mao, Shenghan;Sun, Hongxin;Huang, Fuquan;Wang, Yuanchen;Zhang, Deyu;Wang, Qiwen;Li, Zhaoshen;Zou, Wenbin;Liao, Zhuan
The pathogenesis of pancreatitis involves diverse environmental risk factors, some of which have not yet been clearly elucidated. This study systematically investigated the causal effects of genetically predicted modifiable risk factors on pancreatitis using the Mendelian randomization (MR) approach. Genetic variants associated with 30 exposure factors were obtained from genome-wide association studies. Summary-level statistical data for acute pancreatitis (AP), chronic pancreatitis (CP), alcohol-induced AP (AAP) and alcohol-induced CP (ACP) were obtained from FinnGen consortia. Univariable and multivariable MR analyses were performed to identify causal risk factors for pancreatitis. Genetic predisposition to smoking (OR = 1.314, P = 0.021), cholelithiasis (OR = 1.365, P = 1.307E-19) and inflammatory bowel disease (IBD) (OR = 1.063, P = 0.008) as well as higher triglycerides (OR = 1.189, P = 0.016), body mass index (BMI) (OR = 1.335, P = 3.077E-04), whole body fat mass (OR = 1.291, P = 0.004) and waist circumference (OR = 1.466, P = 0.011) were associated with increased risk of AP. The effect of obesity traits on AP was attenuated after correcting for cholelithiasis. Genetically-driven smoking (OR = 1.595, P = 0.005), alcohol consumption (OR = 3.142, P = 0.020), cholelithiasis (OR = 1.180, P = 0.001), autoimmune diseases (OR = 1.123, P = 0.008), IBD (OR = 1.066, P = 0.042), type 2 diabetes (OR = 1.121, P = 0.029), and higher serum calcium (OR = 1.933, P = 0.018), triglycerides (OR = 1.222, P = 0.021) and waist-to-hip ratio (OR = 1.632, P = 0.023) increased the risk of CP. Cholelithiasis, triglycerides and the waist-to-hip ratio remained significant predictors in the multivariable MR. Genetically predicted alcohol drinking was associated with increased risk of AAP (OR = 15.045, P = 0.001) and ACP (OR = 6.042, P = 0.014). After adjustment of alcohol drinking, genetic liability to IBD had a similar significant causal effect on AAP (OR = 1.137, P = 0.049), while testosterone (OR = 0.270, P = 0.002) a triglyceride (OR = 1.610, P = 0.001) and hip circumference (OR = 0.648, P = 0.040) were significantly associated with ACP. Genetically predicted higher education and household income levels could lower the risk of pancreatitis. This MR study provides evidence of complex causal associations between modifiable risk factors and pancreatitis. These findings provide new insights into potential therapeutic and prevention strategies.
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基因发现和多基因预测，从基因组全基因组协会的教育程度研究中，有110万个人。
影响因子：
30.8
作者：
Lee JJ;Wedow R;Okbay A;Kong E;Maghzian O;Zacher M;Nguyen-Viet TA;Bowers P;Sidorenko J;Karlsson Linnér R;Fontana MA;Kundu T;Lee C;Li H;Li R;Royer R;Timshel PN;Walters RK;Willoughby EA;Yengo L;23andMe Research Team;COGENT (Cognitive Genomics Consortium);Social Science Genetic Association Consortium;Alver M;Bao Y;Clark DW;Day FR;Furlotte NA;Joshi PK;Kemper KE;Kleinman A;Langenberg C;Mägi R;Trampush JW;Verma SS;Wu Y;Lam M;Zhao JH;Zheng Z;Boardman JD;Campbell H;Freese J;Harris KM;Hayward C;Herd P;Kumari M;Lencz T;Luan J;Malhotra AK;Metspalu A;Milani L;Ong KK;Perry JRB;Porteous DJ;Ritchie MD;Smart MC;Smith BH;Tung JY;Wareham NJ;Wilson JF;Beauchamp JP;Conley DC;Esko T;Lehrer SF;Magnusson PKE;Oskarsson S;Pers TH;Robinson MR;Thom K;Watson C;Chabris CF;Meyer MN;Laibson DI;Yang J;Johannesson M;Koellinger PD;Turley P;Visscher PM;Benjamin DJ;Cesarini D
通讯作者：
Cesarini D
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：
2.1
作者：
Bowden J;Davey Smith G;Haycock PC;Burgess S
通讯作者：
Burgess S
影响因子：
13.5
作者：
Chen, Lanlan;Yang, Hongqun;Li, Haitao;He, Chang;Yang, Liu;Lv, Guoyue
通讯作者：
Lv, Guoyue
影响因子：
2.8
作者：
Hong W;Zimmer V;Stock S;Zippi M;Omoshoro-Jones JA;Zhou M
通讯作者：
Zhou M