Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction
Lyytikäinen LP; Kähönen M; Havulinna AS; Maan AC; Brody JA; Olesen M; Bis JC; Schramm K; Isaacs A; Rudan I; Yao J; Gögele M; De Grandi A; Ryan K; Shuldiner AR; Gustav Smith J; Kooperberg C; Van Duijvenboden S; Sinagra G; Benjamin EJ; Kerr KF; Felix SB; Cucca F; Lin HJ; Lin H; Campbell H; Thorolfsdottir RB; Stefansson K; Boutin T; Aeschbacher S; Ribeiro ALP; Arnar DO; Polasek O; Taylor KD; Warren HR; Nelson CP; Wilson JF; Lima-Costa MF; Meitinger T; Assa S; Rice K; Souza RP; Mei H; Levy D; Heckbert SR; Harris TB; Smith AV; Morris AP; Montasser ME; Lambiase PD; Lubitz SA; Mishra PP; Ntalla I; Raitakari OT; Benjamin Shoemaker M; Soliman EZ; Seyerle AA; Concas MP; Barnes CLK; Sotoodehnia N; Noordam R; Joshi PK; Haessler J; Kolcic I; Gudnason V; Jula A; Huang PL; Gasparini P; van Duijn CM; London B; Reiner AP; Völker U; Mook-Kanamori DO; Kääb S; Del Greco M F; Thorleifsson G; Lunetta KL; Cutler MJ; Ellinor PT; O'Connell JR; Spector TD; Newton-Cheh CH; van den Berg ME; Uitterlinden A; Weiss S; de Mutsert R; Dominiczak A; Conen D; Salomaa V; Gudbjartsson DF; Wouter Jukema J; Thériault S; Munroe PB; Nikus K; Launer LJ; Sulem P; Strauch K; Rotter JI; Mahajan A; Giedraitis V; Cranley JJ; Riaz MB; Barnes MR; Tarasov KV; Psaty BM; Guo X; Thorsteinsdottir U; Gogarten SM; Stricker BH; Sveinbjornsson G; Fuchsberger C; Arking DE; Correa A; Ramirez J; Caulfield MJ; Choi SH; Smith BH; Boerwinkle E; Peters U; Ingelsson E; Qian Y; Marten J; Risch L; Avery CL; Araujo NM; Weng LC; Sääksjärvi K; Lakatta EG; Porteous DJ; Foco L; Dörr M; Tucker NR; van de Vegte YJ; Macfarlane PW; Kors JA; Ehret GB; Mifsud B; Roden DM; Mangino M; Ford I; Jamshidi Y; Cartwright JH; Lind L; Yldau van der Ende M; Pramstaller PP; Verweij N; Pattaro C; Nadkarni GN; Biggs ML; Lehtimäki T; Murray AD; Laurie CC; Whitsel EA; Tinker A; Hayward C; Alonso A; Cook JP; Samani NJ; Wilson J; Preuss MH; Loos RJF; Roselli C; Holm H; van der Harst P; Hicks AA; Trompet S; Chaffin MD; Orini M; Padmanabhan S; Sundström J; Bottinger EP; Waldenberger M; Jackson RD; Rienstra M; Ulivi S; Müller-Nurasyid M; Stilp A; Fatkin D; Mononen N; Abdullah Said M; Tarazona-Santos E; Peters A; Hall AW; Lindgren CM; Ding J; Hutri-Kähönen N; Sinner MF
https://urn.fi/URN:NBN:fi-fe2021042822286
Tiivistelmä
The electrocardiographic PR interval reflects atrioventricular
conduction, and is associated with conduction abnormalities, pacemaker
implantation, atrial fibrillation (AF), and cardiovascular mortality.
Here we report a multi-ancestry (N = 293,051) genome-wide association
meta-analysis for the PR interval, discovering 202 loci of which 141
have not previously been reported. Variants at identified loci increase
the percentage of heritability explained, from 33.5% to 62.6%. We
observe enrichment for cardiac muscle developmental/contractile and
cytoskeletal genes, highlighting key regulation processes for
atrioventricular conduction. Additionally, 8 loci not previously
reported harbor genes underlying inherited arrhythmic syndromes and/or
cardiomyopathies suggesting a role for these genes in cardiovascular
pathology in the general population. We show that polygenic
predisposition to PR interval duration is an endophenotype for
cardiovascular disease, including distal conduction disease, AF, and
atrioventricular pre-excitation. These findings advance our
understanding of the polygenic basis of cardiac conduction, and the
genetic relationship between PR interval duration and cardiovascular
disease.
Kokoelmat
- Rinnakkaistallenteet [19207]