Discovery of novel heart rate-associated loci using the Exome Chip
Hagemeijer Y; Guo XQ; Rosand J; Psaty BM; Grarup N; Taylor KD; Pistis G; Shah N; Cabrera CP; Hayward C; Rudan I; Lin HH; Eppinga RN; Mangino M; Prins BP; Hall LM; Porteous DJ; Mook-Kanamori DO; Asselbergs FW; Deloukas P; Wilson J; Roselli C; Harris TB; Qi LH; Eijgelsheim M; Li M; Soliman EZ; Arking DE; Doney ASF; Caulfield MJ; Padmanabhan S; Yao J; Stirrups KE; Kääb S; Jukema JW; Marten J; Xie ZJ; de Mutsert R; Sotoodehnia N; Li-Gao RF; Isaacs A; Gudnason V; Sinner MF; Kooperberg C; Völker U; O'Donnell CJ; Jamshidi Y; Samani NJ; Kanters JK; Uitterlinden A; Murray AD; Pedersen O; Morris AD; Raitakari OT; Fu YP; Sanna S; Ellinor PT; Kors JA; Mifsud B; Dedoussis G; van Duijn CM; Zoledziewska M; Hoes AW; Waldenberger M; Tobin MD; Spector TD; van der Meer P; de Haan HG; Felix SB; Palmer CNA; Müller-Nurasyid M; Silva CT; Launer LJ; Sattar N; Lin HJ; Haessler J; Peters A; Lehtimäki T; Stanton AV; Mulas A; Bihlmeyer NA; Kolcic I; Lubitz SA; Trompet S; Tinker A; van der Harst P; Brody JA; Sever P; van den Berg ME; Poulter N; Lyytikainen LP; Rotter JI; Hwang SJ; Macfarlane PW; Stricker BH; Zeggini E; Munroe PB; de Boer R; Verweij N; Dörr M; Rivadeneira F; Hansen T; Weiss S; Vaartjes I; Heckbert SR; Liu SM; Mei H; Radmanesh F; Alonso A; van Setten J; Orrú M; Entwistle A; Nelson CP; Smith AV; Dominiczak AF; Linneberg A; Polasek O; Warren HR; Bis JC; Huang PL; Kähönen M
Discovery of novel heart rate-associated loci using the Exome Chip
Hagemeijer Y
Guo XQ
Rosand J
Psaty BM
Grarup N
Taylor KD
Pistis G
Shah N
Cabrera CP
Hayward C
Rudan I
Lin HH
Eppinga RN
Mangino M
Prins BP
Hall LM
Porteous DJ
Mook-Kanamori DO
Asselbergs FW
Deloukas P
Wilson J
Roselli C
Harris TB
Qi LH
Eijgelsheim M
Li M
Soliman EZ
Arking DE
Doney ASF
Caulfield MJ
Padmanabhan S
Yao J
Stirrups KE
Kääb S
Jukema JW
Marten J
Xie ZJ
de Mutsert R
Sotoodehnia N
Li-Gao RF
Isaacs A
Gudnason V
Sinner MF
Kooperberg C
Völker U
O'Donnell CJ
Jamshidi Y
Samani NJ
Kanters JK
Uitterlinden A
Murray AD
Pedersen O
Morris AD
Raitakari OT
Fu YP
Sanna S
Ellinor PT
Kors JA
Mifsud B
Dedoussis G
van Duijn CM
Zoledziewska M
Hoes AW
Waldenberger M
Tobin MD
Spector TD
van der Meer P
de Haan HG
Felix SB
Palmer CNA
Müller-Nurasyid M
Silva CT
Launer LJ
Sattar N
Lin HJ
Haessler J
Peters A
Lehtimäki T
Stanton AV
Mulas A
Bihlmeyer NA
Kolcic I
Lubitz SA
Trompet S
Tinker A
van der Harst P
Brody JA
Sever P
van den Berg ME
Poulter N
Lyytikainen LP
Rotter JI
Hwang SJ
Macfarlane PW
Stricker BH
Zeggini E
Munroe PB
de Boer R
Verweij N
Dörr M
Rivadeneira F
Hansen T
Weiss S
Vaartjes I
Heckbert SR
Liu SM
Mei H
Radmanesh F
Alonso A
van Setten J
Orrú M
Entwistle A
Nelson CP
Smith AV
Dominiczak AF
Linneberg A
Polasek O
Warren HR
Bis JC
Huang PL
Kähönen M
OXFORD UNIV PRESS
Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2021042716888
https://urn.fi/URN:NBN:fi-fe2021042716888
Tiivistelmä
Resting heart rate is a heritable trait, and an increase in heart rate is associated with increased mortality risk. Genome-wide association study analyses have found loci associated with resting heart rate, at the time of our study these loci explained 0.9% of the variation. This study aims to discover new genetic loci associated with heart rate from Exome Chip meta-analyses. Heart rate was measured from either elecrtrocardiograms or pulse recordings. We meta-analysed heart rate association results from 104 452 European-ancestry individuals from 30 cohorts, genotyped using the Exome Chip. Twenty-four variants were selected for follow-up in an independent dataset (UK Biobank, N = 134 251). Conditional and gene-based testing was undertaken, and variants were investigated with bioinformatics methods.We discovered five novel heart rate loci, and one new independent low-frequency non-synonymous variant in an established heart rate locus (KIAA1755). Lead variants in four of the novel loci are non-synonymous variants in the genes C10orf71, DALDR3, TESK2 and SEC31B. The variant at SEC31B is significantly associated with SEC31B expression in heart and tibial nerve tissue. Further candidate genes were detected from long-range regulatory chromatin interactions in heart tissue (SCD, SLF2 and MAPK8). We observed significant enrichment in DNase I hypersensitive sites in fetal heart and lung. Moreover, enrichment was seen for the first time in human neuronal progenitor cells (derived from embryonic stem cells) and fetal muscle samples by including our novel variants.Our findings advance the knowledge of the genetic architecture of heart rate, and indicate new candidate genes for follow-up functional studies.
Kokoelmat
- Rinnakkaistallenteet [19207]