PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity

van Setten J; Brody JA; Jamshidi Y; Swenson BR; Butler AM; Campbell H; Del Greco FM; Evans DS; Gibson Q; Gudbjartsson DF; Kerr KF; Krijthe BP; Lyytikainen LP; Muller C; Muller-Nurasyid M; Nolte IM; Padmanabhan S; Ritchie MD; Robino A; Smith AV; Steri M; Tanaka T; Teumer A; Trompet S; Ulivi S; Verweij N; Yin XY; Arnar DO; Asselbergs FW; Bader JS; Barnard J; Bis J; Blankenberg S; Boerwinkle E; Bradford Y; Buckley BM; Chung MK; Crawford D; den Hoed M; Denny JC; Dominiczak AF; Ehret GB; Eijgelsheim M; Ellinor PT; Felix SB; Franco OH; Franke L; Harris TB; Holm H; Ilaria G; Iorio A; Kahonen M; Kolcic I; Kors JA; Lakatta EG; Launer LJ; Lin HH; Lin HJ; Loos RJF; Lubitz SA; Macfarlane PW; Magnani JW; Leach IM; Meitinger T; Mitchell BD; Munzel T; Papanicolaou GJ; Peters A; Pfeufer A; Pramstaller PP; Raitakari OT; Rotter JI; Rudan I; Samani NJ; Schlessinger D; Aldana CTS; Sinner MF; Smith JD; Snieder H; Soliman EZ; Spector TD; Stott DJ; Strauch K; Tarasov KV; Thorsteinsdottir U; Uitterlinden AG; Van Wagoner DR; Volker U; Volzke H; Waldenberger M; Westra HJ; Wild PS; Zeller T; Alonso A; Avery CL; Bandinelli S; Benjamin EJ; Cucca F; Dorr M; Ferrucci L; Gasparini P; Gudnason V; Hayward C; Heckbert SR; Hicks AA; Jukema JW; Kaab S; Lehtimaki T; Liu YM; Munroe PB; Parsa A; Polasek O; Psaty BM; Roden DM; Schnabel RB; Sinagra G; Stefansson K; Stricker BH; van der Harst P; van Duijn CM; Wilson JF; Gharib SA; de Bakker PIW; Isaacs A; Arking DE; Sotoodehnia N; Sotoodehnia N; Arking DE; Isaacs A; de Bakker PIW; Gharib SA; Wilson JF
PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity

van Setten J
Brody JA
Jamshidi Y
Swenson BR
Butler AM
Campbell H
Del Greco FM
Evans DS
Gibson Q
Gudbjartsson DF
Kerr KF
Krijthe BP
Lyytikainen LP
Muller C
Muller-Nurasyid M
Nolte IM
Padmanabhan S
Ritchie MD
Robino A
Smith AV
Steri M
Tanaka T
Teumer A
Trompet S
Ulivi S
Verweij N
Yin XY
Arnar DO
Asselbergs FW
Bader JS
Barnard J
Bis J
Blankenberg S
Boerwinkle E
Bradford Y
Buckley BM
Chung MK
Crawford D
den Hoed M
Denny JC
Dominiczak AF
Ehret GB
Eijgelsheim M
Ellinor PT
Felix SB
Franco OH
Franke L
Harris TB
Holm H
Ilaria G
Iorio A
Kahonen M
Kolcic I
Kors JA
Lakatta EG
Launer LJ
Lin HH
Lin HJ
Loos RJF
Lubitz SA
Macfarlane PW
Magnani JW
Leach IM
Meitinger T
Mitchell BD
Munzel T
Papanicolaou GJ
Peters A
Pfeufer A
Pramstaller PP
Raitakari OT
Rotter JI
Rudan I
Samani NJ
Schlessinger D
Aldana CTS
Sinner MF
Smith JD
Snieder H
Soliman EZ
Spector TD
Stott DJ
Strauch K
Tarasov KV
Thorsteinsdottir U
Uitterlinden AG
Van Wagoner DR
Volker U
Volzke H
Waldenberger M
Westra HJ
Wild PS
Zeller T
Alonso A
Avery CL
Bandinelli S
Benjamin EJ
Cucca F
Dorr M
Ferrucci L
Gasparini P
Gudnason V
Hayward C
Heckbert SR
Hicks AA
Jukema JW
Kaab S
Lehtimaki T
Liu YM
Munroe PB
Parsa A
Polasek O
Psaty BM
Roden DM
Schnabel RB
Sinagra G
Stefansson K
Stricker BH
van der Harst P
van Duijn CM
Wilson JF
Gharib SA
de Bakker PIW
Isaacs A
Arking DE
Sotoodehnia N
Sotoodehnia N
Arking DE
Isaacs A
de Bakker PIW
Gharib SA
Wilson JF
Katso/Avaa
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NATURE PUBLISHING GROUP
doi:10.1038/s41467-018-04766-9
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Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2021042719557
Tiivistelmä
Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genomewide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Examination of these loci reveals known and previously not-yet-reported biological processes involved in cardiac atrial electrical activity. Genes in these loci are overrepresented in cardiac disease processes including heart block and atrial fibrillation. Variants in over half of the 44 loci were associated with atrial or blood transcript expression levels, or were in high linkage disequilibrium with missense variants. Six additional loci were identified either by meta-analysis of similar to 105,000 African and European-descent individuals and/or by pleiotropic analyses combining PR interval with heart rate, QRS interval, and atrial fibrillation. These findings implicate developmental pathways, and identify transcription factors, ionchannel genes, and cell-junction/cell-signaling proteins in atrio-ventricular conduction, identifying potential targets for drug development.
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