Genetic associations for two biological age measures point to distinct aging phenotypes.
Genetic associations for two biological age measures point to distinct aging phenotypes.
复制标题
两种生物年龄指标的遗传关联指向不同的衰老表型。
DOI:
10.1111/acel.13376
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发表时间:
2021-06
期刊:
影响因子:
7.8
通讯作者:
Levine ME
中科院分区:
文献类型:
--
作者:
Kuo CL;Pilling LC;Liu Z;Atkins JL;Levine ME
Biological age measures outperform chronological age in predicting various aging outcomes, yet little is known regarding genetic predisposition. We performed genome‐wide association scans of two age‐adjusted biological age measures (PhenoAgeAcceleration and BioAgeAcceleration), estimated from clinical biochemistry markers (Levine et al., 2018; Levine, 2013) in European‐descent participants from UK Biobank. The strongest signals were found in the APOE gene, tagged by the two major protein‐coding SNPs, PhenoAgeAccel—rs429358 (APOE e4 determinant) (p = 1.50 × 10−72); BioAgeAccel—rs7412 (APOE e2 determinant) (p = 3.16 × 10−60). Interestingly, we observed inverse APOE e2 and e4 associations and unique pathway enrichments when comparing the two biological age measures. Genes associated with BioAgeAccel were enriched in lipid related pathways, while genes associated with PhenoAgeAccel showed enrichment for immune system, cell function, and carbohydrate homeostasis pathways, suggesting the two measures capture different aging domains. Our study reaffirms that aging patterns are heterogeneous across individuals, and the manner in which a person ages may be partly attributed to genetic predisposition. A genome‐wide association study for differences in aging rates was performed in the UK Biobank sample using two previously established aging measures. Results suggest that one was associated with genes involved in lipid metabolism and blood pressure, while the other was associated with genes involved in immune functioning. APOE e4 was associated with faster aging in the measure reflecting lipid age, yet paradoxically, was associated with reduced aging in the measure reflecting immune functioning and inflammation.
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影响因子:
64.8
作者:
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者:
Marchini J
影响因子:
5
作者:
Fry A;Littlejohns TJ;Sudlow C;Doherty N;Adamska L;Sprosen T;Collins R;Allen NE
通讯作者:
Allen NE
影响因子:
64.8
作者:
Michailidou K;Lindström S;Dennis J;Beesley J;Hui S;Kar S;Lemaçon A;Soucy P;Glubb D;Rostamianfar A;Bolla MK;Wang Q;Tyrer J;Dicks E;Lee A;Wang Z;Allen J;Keeman R;Eilber U;French JD;Qing Chen X;Fachal L;McCue K;McCart Reed AE;Ghoussaini M;Carroll JS;Jiang X;Finucane H;Adams M;Adank MA;Ahsan H;Aittomäki K;Anton-Culver H;Antonenkova NN;Arndt V;Aronson KJ;Arun B;Auer PL;Bacot F;Barrdahl M;Baynes C;Beckmann MW;Behrens S;Benitez J;Bermisheva M;Bernstein L;Blomqvist C;Bogdanova NV;Bojesen SE;Bonanni B;Børresen-Dale AL;Brand JS;Brauch H;Brennan P;Brenner H;Brinton L;Broberg P;Brock IW;Broeks A;Brooks-Wilson A;Brucker SY;Brüning T;Burwinkel B;Butterbach K;Cai Q;Cai H;Caldés T;Canzian F;Carracedo A;Carter BD;Castelao JE;Chan TL;David Cheng TY;Seng Chia K;Choi JY;Christiansen H;Clarke CL;NBCS Collaborators;Collée M;Conroy DM;Cordina-Duverger E;Cornelissen S;Cox DG;Cox A;Cross SS;Cunningham JM;Czene K;Daly MB;Devilee P;Doheny KF;Dörk T;Dos-Santos-Silva I;Dumont M;Durcan L;Dwek M;Eccles DM;Ekici AB;Eliassen AH;Ellberg C;Elvira M;Engel C;Eriksson M;Fasching PA;Figueroa J;Flesch-Janys D;Fletcher O;Flyger H;Fritschi L;Gaborieau V;Gabrielson M;Gago-Dominguez M;Gao YT;Gapstur SM;García-Sáenz JA;Gaudet MM;Georgoulias V;Giles GG;Glendon G;Goldberg MS;Goldgar DE;González-Neira A;Grenaker Alnæs GI;Grip M;Gronwald J;Grundy A;Guénel P;Haeberle L;Hahnen E;Haiman CA;Håkansson N;Hamann U;Hamel N;Hankinson S;Harrington P;Hart SN;Hartikainen JM;Hartman M;Hein A;Heyworth J;Hicks B;Hillemanns P;Ho DN;Hollestelle A;Hooning MJ;Hoover RN;Hopper JL;Hou MF;Hsiung CN;Huang G;Humphreys K;Ishiguro J;Ito H;Iwasaki M;Iwata H;Jakubowska A;Janni W;John EM;Johnson N;Jones K;Jones M;Jukkola-Vuorinen A;Kaaks R;Kabisch M;Kaczmarek K;Kang D;Kasuga Y;Kerin MJ;Khan S;Khusnutdinova E;Kiiski JI;Kim SW;Knight JA;Kosma VM;Kristensen VN;Krüger U;Kwong A;Lambrechts D;Le Marchand L;Lee E;Lee MH;Lee JW;Neng Lee C;Lejbkowicz F;Li J;Lilyquist J;Lindblom A;Lissowska J;Lo WY;Loibl S;Long J;Lophatananon A;Lubinski J;Luccarini C;Lux MP;Ma ESK;MacInnis RJ;Maishman T;Makalic E;Malone KE;Kostovska IM;Mannermaa A;Manoukian S;Manson JE;Margolin S;Mariapun S;Martinez ME;Matsuo K;Mavroudis D;McKay J;McLean C;Meijers-Heijboer H;Meindl A;Menéndez P;Menon U;Meyer J;Miao H;Miller N;Taib NAM;Muir K;Mulligan AM;Mulot C;Neuhausen SL;Nevanlinna H;Neven P;Nielsen SF;Noh DY;Nordestgaard BG;Norman A;Olopade OI;Olson JE;Olsson H;Olswold C;Orr N;Pankratz VS;Park SK;Park-Simon TW;Lloyd R;Perez JIA;Peterlongo P;Peto J;Phillips KA;Pinchev M;Plaseska-Karanfilska D;Prentice R;Presneau N;Prokofyeva D;Pugh E;Pylkäs K;Rack B;Radice P;Rahman N;Rennert G;Rennert HS;Rhenius V;Romero A;Romm J;Ruddy KJ;Rüdiger T;Rudolph A;Ruebner M;Rutgers EJT;Saloustros E;Sandler DP;Sangrajrang S;Sawyer EJ;Schmidt DF;Schmutzler RK;Schneeweiss A;Schoemaker MJ;Schumacher F;Schürmann P;Scott RJ;Scott C;Seal S;Seynaeve C;Shah M;Sharma P;Shen CY;Sheng G;Sherman ME;Shrubsole MJ;Shu XO;Smeets A;Sohn C;Southey MC;Spinelli JJ;Stegmaier C;Stewart-Brown S;Stone J;Stram DO;Surowy H;Swerdlow A;Tamimi R;Taylor JA;Tengström M;Teo SH;Beth Terry M;Tessier DC;Thanasitthichai S;Thöne K;Tollenaar RAEM;Tomlinson I;Tong L;Torres D;Truong T;Tseng CC;Tsugane S;Ulmer HU;Ursin G;Untch M;Vachon C;van Asperen CJ;Van Den Berg D;van den Ouweland AMW;van der Kolk L;van der Luijt RB;Vincent D;Vollenweider J;Waisfisz Q;Wang-Gohrke S;Weinberg CR;Wendt C;Whittemore AS;Wildiers H;Willett W;Winqvist R;Wolk A;Wu AH;Xia L;Yamaji T;Yang XR;Har Yip C;Yoo KY;Yu JC;Zheng W;Zheng Y;Zhu B;Ziogas A;Ziv E;ABCTB Investigators;ConFab/AOCS Investigators;Lakhani SR;Antoniou AC;Droit A;Andrulis IL;Amos CI;Couch FJ;Pharoah PDP;Chang-Claude J;Hall P;Hunter DJ;Milne RL;García-Closas M;Schmidt MK;Chanock SJ;Dunning AM;Edwards SL;Bader GD;Chenevix-Trench G;Simard J;Kraft P;Easton DF
通讯作者:
Easton DF
影响因子:
30.8
作者:
Mahajan A;Taliun D;Thurner M;Robertson NR;Torres JM;Rayner NW;Payne AJ;Steinthorsdottir V;Scott RA;Grarup N;Cook JP;Schmidt EM;Wuttke M;Sarnowski C;Mägi R;Nano J;Gieger C;Trompet S;Lecoeur C;Preuss MH;Prins BP;Guo X;Bielak LF;Below JE;Bowden DW;Chambers JC;Kim YJ;Ng MCY;Petty LE;Sim X;Zhang W;Bennett AJ;Bork-Jensen J;Brummett CM;Canouil M;Ec Kardt KU;Fischer K;Kardia SLR;Kronenberg F;Läll K;Liu CT;Locke AE;Luan J;Ntalla I;Nylander V;Schönherr S;Schurmann C;Yengo L;Bottinger EP;Brandslund I;Christensen C;Dedoussis G;Florez JC;Ford I;Franco OH;Frayling TM;Giedraitis V;Hackinger S;Hattersley AT;Herder C;Ikram MA;Ingelsson M;Jørgensen ME;Jørgensen T;Kriebel J;Kuusisto J;Ligthart S;Lindgren CM;Linneberg A;Lyssenko V;Mamakou V;Meitinger T;Mohlke KL;Morris AD;Nadkarni G;Pankow JS;Peters A;Sattar N;Stančáková A;Strauch K;Taylor KD;Thorand B;Thorleifsson G;Thorsteinsdottir U;Tuomilehto J;Witte DR;Dupuis J;Peyser PA;Zeggini E;Loos RJF;Froguel P;Ingelsson E;Lind L;Groop L;Laakso M;Collins FS;Jukema JW;Palmer CNA;Grallert H;Metspalu A;Dehghan A;Köttgen A;Abecasis GR;Meigs JB;Rotter JI;Marchini J;Pedersen O;Hansen T;Langenberg C;Wareham NJ;Stefansson K;Gloyn AL;Morris AP;Boehnke M;McCarthy MI
通讯作者:
McCarthy MI
影响因子:
30.8
作者:
Bulik-Sullivan, Brendan K.;Loh, Po-Ru;Finucane, Hilary K.;Ripke, Stephan;Yang, Jian;Patterson, Nick;Daly, Mark J.;Price, Alkes L.;Neale, Benjamin M.
通讯作者:
Neale, Benjamin M.