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

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

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