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Fine-mapping, novel loci identification, and SNP association transferability in a genome-wide association study of QRS duration in African Americans

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Fine-mapping, novel loci identification, and SNP association transferability in a genome-wide association study of QRS duration in African Americans. / Evans, Daniel S; Avery, Christy L; Nalls, Mike A; Li, Guo; Barnard, John; Smith, Erin N; Tanaka, Toshiko; Butler, Anne M; Buxbaum, Sarah G; Alonso, Alvaro; Arking, Dan E; Berenson, Gerald S; Bis, Joshua C; Buyske, Steven; Carty, Cara L; Chen, Wei; Chung, Mina K; Cummings, Steven R; Deo, Rajat; Eaton, Charles B; Fox, Ervin R; Heckbert, Susan R; Heiss, Gerardo; Hindorff, Lucia A; Hsueh, Wen-Chi; Isaacs, Aaron; Jamshidi, Yalda; Kerr, Kathleen F; Liu, Felix; Liu, Yongmei; Lohman, Kurt K; Magnani, Jared W; Maher, Joseph F; Mehra, Reena; Meng, Yan A; Musani, Solomon K; Newton-Cheh, Christopher; North, Kari E; Psaty, Bruce M; Redline, Susan; Rotter, Jerome I; Schnabel, Renate B; Schork, Nicholas J; Shohet, Ralph V; Singleton, Andrew B; Smith, Jonathan D; Soliman, Elsayed Z; Srinivasan, Sathanur R; Taylor, Herman A; Van Wagoner, David R; Wilson, James G; Young, Taylor; Zhang, Zhu-Ming; Zonderman, Alan B; Evans, Michele K; Ferrucci, Luigi; Murray, Sarah S; Tranah, Gregory J; Whitsel, Eric A; Reiner, Alex P; Sotoodehnia, Nona; CHARGE QRS Consortium.

in: HUM MOL GENET, Jahrgang 25, Nr. 19, 01.10.2016, S. 4350-4368.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Evans, DS, Avery, CL, Nalls, MA, Li, G, Barnard, J, Smith, EN, Tanaka, T, Butler, AM, Buxbaum, SG, Alonso, A, Arking, DE, Berenson, GS, Bis, JC, Buyske, S, Carty, CL, Chen, W, Chung, MK, Cummings, SR, Deo, R, Eaton, CB, Fox, ER, Heckbert, SR, Heiss, G, Hindorff, LA, Hsueh, W-C, Isaacs, A, Jamshidi, Y, Kerr, KF, Liu, F, Liu, Y, Lohman, KK, Magnani, JW, Maher, JF, Mehra, R, Meng, YA, Musani, SK, Newton-Cheh, C, North, KE, Psaty, BM, Redline, S, Rotter, JI, Schnabel, RB, Schork, NJ, Shohet, RV, Singleton, AB, Smith, JD, Soliman, EZ, Srinivasan, SR, Taylor, HA, Van Wagoner, DR, Wilson, JG, Young, T, Zhang, Z-M, Zonderman, AB, Evans, MK, Ferrucci, L, Murray, SS, Tranah, GJ, Whitsel, EA, Reiner, AP, Sotoodehnia, N & CHARGE QRS Consortium 2016, 'Fine-mapping, novel loci identification, and SNP association transferability in a genome-wide association study of QRS duration in African Americans', HUM MOL GENET, Jg. 25, Nr. 19, S. 4350-4368. https://doi.org/10.1093/hmg/ddw284

APA

Evans, D. S., Avery, C. L., Nalls, M. A., Li, G., Barnard, J., Smith, E. N., Tanaka, T., Butler, A. M., Buxbaum, S. G., Alonso, A., Arking, D. E., Berenson, G. S., Bis, J. C., Buyske, S., Carty, C. L., Chen, W., Chung, M. K., Cummings, S. R., Deo, R., ... CHARGE QRS Consortium (2016). Fine-mapping, novel loci identification, and SNP association transferability in a genome-wide association study of QRS duration in African Americans. HUM MOL GENET, 25(19), 4350-4368. https://doi.org/10.1093/hmg/ddw284

Vancouver

Evans DS, Avery CL, Nalls MA, Li G, Barnard J, Smith EN et al. Fine-mapping, novel loci identification, and SNP association transferability in a genome-wide association study of QRS duration in African Americans. HUM MOL GENET. 2016 Okt 1;25(19):4350-4368. https://doi.org/10.1093/hmg/ddw284

Bibtex

@article{436700577e5944d09c3ebb6b5a2e67a3,
title = "Fine-mapping, novel loci identification, and SNP association transferability in a genome-wide association study of QRS duration in African Americans",
abstract = "The electrocardiographic QRS duration, a measure of ventricular depolarization and conduction, is associated with cardiovascular mortality. While single nucleotide polymorphisms (SNPs) associated with QRS duration have been identified at 22 loci in populations of European descent, the genetic architecture of QRS duration in non-European populations is largely unknown. We therefore performed a genome-wide association study (GWAS) meta-analysis of QRS duration in 13,031 African Americans from ten cohorts and a transethnic GWAS meta-analysis with additional results from populations of European descent. In the African American GWAS, a single genome-wide significant SNP association was identified (rs3922844, P = 4 × 10-14) in intron 16 of SCN5A, a voltage-gated cardiac sodium channel gene. The QRS-prolonging rs3922844 C allele was also associated with decreased SCN5A RNA expression in human atrial tissue (P = 1.1 × 10-4). High density genotyping revealed that the SCN5A association region in African Americans was confined to intron 16. Transethnic GWAS meta-analysis identified novel SNP associations on chromosome 18 in MYL12A (rs1662342, P = 4.9 × 10-8) and chromosome 1 near CD1E and SPTA1 (rs7547997, P = 7.9 × 10-9). The 22 QRS loci previously identified in populations of European descent were enriched for significant SNP associations with QRS duration in African Americans (P = 9.9 × 10-7), and index SNP associations in or near SCN5A, SCN10A, CDKN1A, NFIA, HAND1, TBX5 and SETBP1 replicated in African Americans. In summary, rs3922844 was associated with QRS duration and SCN5A expression, two novel QRS loci were identified using transethnic meta-analysis, and a significant proportion of QRS-SNP associations discovered in populations of European descent were transferable to African Americans when adequate power was achieved.",
keywords = "African Americans/genetics, Alleles, Cardiovascular Diseases/genetics, Electrocardiography, European Continental Ancestry Group/genetics, Female, Genome-Wide Association Study, Genotype, Heart Ventricles/physiopathology, Humans, Male, Myocardium/pathology, NAV1.5 Voltage-Gated Sodium Channel/genetics, Polymorphism, Single Nucleotide/genetics",
author = "Evans, {Daniel S} and Avery, {Christy L} and Nalls, {Mike A} and Guo Li and John Barnard and Smith, {Erin N} and Toshiko Tanaka and Butler, {Anne M} and Buxbaum, {Sarah G} and Alvaro Alonso and Arking, {Dan E} and Berenson, {Gerald S} and Bis, {Joshua C} and Steven Buyske and Carty, {Cara L} and Wei Chen and Chung, {Mina K} and Cummings, {Steven R} and Rajat Deo and Eaton, {Charles B} and Fox, {Ervin R} and Heckbert, {Susan R} and Gerardo Heiss and Hindorff, {Lucia A} and Wen-Chi Hsueh and Aaron Isaacs and Yalda Jamshidi and Kerr, {Kathleen F} and Felix Liu and Yongmei Liu and Lohman, {Kurt K} and Magnani, {Jared W} and Maher, {Joseph F} and Reena Mehra and Meng, {Yan A} and Musani, {Solomon K} and Christopher Newton-Cheh and North, {Kari E} and Psaty, {Bruce M} and Susan Redline and Rotter, {Jerome I} and Schnabel, {Renate B} and Schork, {Nicholas J} and Shohet, {Ralph V} and Singleton, {Andrew B} and Smith, {Jonathan D} and Soliman, {Elsayed Z} and Srinivasan, {Sathanur R} and Taylor, {Herman A} and {Van Wagoner}, {David R} and Wilson, {James G} and Taylor Young and Zhu-Ming Zhang and Zonderman, {Alan B} and Evans, {Michele K} and Luigi Ferrucci and Murray, {Sarah S} and Tranah, {Gregory J} and Whitsel, {Eric A} and Reiner, {Alex P} and Nona Sotoodehnia and {CHARGE QRS Consortium}",
note = "{\textcopyright} The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.",
year = "2016",
month = oct,
day = "1",
doi = "10.1093/hmg/ddw284",
language = "English",
volume = "25",
pages = "4350--4368",
journal = "HUM MOL GENET",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "19",

}

RIS

TY - JOUR

T1 - Fine-mapping, novel loci identification, and SNP association transferability in a genome-wide association study of QRS duration in African Americans

AU - Evans, Daniel S

AU - Avery, Christy L

AU - Nalls, Mike A

AU - Li, Guo

AU - Barnard, John

AU - Smith, Erin N

AU - Tanaka, Toshiko

AU - Butler, Anne M

AU - Buxbaum, Sarah G

AU - Alonso, Alvaro

AU - Arking, Dan E

AU - Berenson, Gerald S

AU - Bis, Joshua C

AU - Buyske, Steven

AU - Carty, Cara L

AU - Chen, Wei

AU - Chung, Mina K

AU - Cummings, Steven R

AU - Deo, Rajat

AU - Eaton, Charles B

AU - Fox, Ervin R

AU - Heckbert, Susan R

AU - Heiss, Gerardo

AU - Hindorff, Lucia A

AU - Hsueh, Wen-Chi

AU - Isaacs, Aaron

AU - Jamshidi, Yalda

AU - Kerr, Kathleen F

AU - Liu, Felix

AU - Liu, Yongmei

AU - Lohman, Kurt K

AU - Magnani, Jared W

AU - Maher, Joseph F

AU - Mehra, Reena

AU - Meng, Yan A

AU - Musani, Solomon K

AU - Newton-Cheh, Christopher

AU - North, Kari E

AU - Psaty, Bruce M

AU - Redline, Susan

AU - Rotter, Jerome I

AU - Schnabel, Renate B

AU - Schork, Nicholas J

AU - Shohet, Ralph V

AU - Singleton, Andrew B

AU - Smith, Jonathan D

AU - Soliman, Elsayed Z

AU - Srinivasan, Sathanur R

AU - Taylor, Herman A

AU - Van Wagoner, David R

AU - Wilson, James G

AU - Young, Taylor

AU - Zhang, Zhu-Ming

AU - Zonderman, Alan B

AU - Evans, Michele K

AU - Ferrucci, Luigi

AU - Murray, Sarah S

AU - Tranah, Gregory J

AU - Whitsel, Eric A

AU - Reiner, Alex P

AU - Sotoodehnia, Nona

AU - CHARGE QRS Consortium

N1 - © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

PY - 2016/10/1

Y1 - 2016/10/1

N2 - The electrocardiographic QRS duration, a measure of ventricular depolarization and conduction, is associated with cardiovascular mortality. While single nucleotide polymorphisms (SNPs) associated with QRS duration have been identified at 22 loci in populations of European descent, the genetic architecture of QRS duration in non-European populations is largely unknown. We therefore performed a genome-wide association study (GWAS) meta-analysis of QRS duration in 13,031 African Americans from ten cohorts and a transethnic GWAS meta-analysis with additional results from populations of European descent. In the African American GWAS, a single genome-wide significant SNP association was identified (rs3922844, P = 4 × 10-14) in intron 16 of SCN5A, a voltage-gated cardiac sodium channel gene. The QRS-prolonging rs3922844 C allele was also associated with decreased SCN5A RNA expression in human atrial tissue (P = 1.1 × 10-4). High density genotyping revealed that the SCN5A association region in African Americans was confined to intron 16. Transethnic GWAS meta-analysis identified novel SNP associations on chromosome 18 in MYL12A (rs1662342, P = 4.9 × 10-8) and chromosome 1 near CD1E and SPTA1 (rs7547997, P = 7.9 × 10-9). The 22 QRS loci previously identified in populations of European descent were enriched for significant SNP associations with QRS duration in African Americans (P = 9.9 × 10-7), and index SNP associations in or near SCN5A, SCN10A, CDKN1A, NFIA, HAND1, TBX5 and SETBP1 replicated in African Americans. In summary, rs3922844 was associated with QRS duration and SCN5A expression, two novel QRS loci were identified using transethnic meta-analysis, and a significant proportion of QRS-SNP associations discovered in populations of European descent were transferable to African Americans when adequate power was achieved.

AB - The electrocardiographic QRS duration, a measure of ventricular depolarization and conduction, is associated with cardiovascular mortality. While single nucleotide polymorphisms (SNPs) associated with QRS duration have been identified at 22 loci in populations of European descent, the genetic architecture of QRS duration in non-European populations is largely unknown. We therefore performed a genome-wide association study (GWAS) meta-analysis of QRS duration in 13,031 African Americans from ten cohorts and a transethnic GWAS meta-analysis with additional results from populations of European descent. In the African American GWAS, a single genome-wide significant SNP association was identified (rs3922844, P = 4 × 10-14) in intron 16 of SCN5A, a voltage-gated cardiac sodium channel gene. The QRS-prolonging rs3922844 C allele was also associated with decreased SCN5A RNA expression in human atrial tissue (P = 1.1 × 10-4). High density genotyping revealed that the SCN5A association region in African Americans was confined to intron 16. Transethnic GWAS meta-analysis identified novel SNP associations on chromosome 18 in MYL12A (rs1662342, P = 4.9 × 10-8) and chromosome 1 near CD1E and SPTA1 (rs7547997, P = 7.9 × 10-9). The 22 QRS loci previously identified in populations of European descent were enriched for significant SNP associations with QRS duration in African Americans (P = 9.9 × 10-7), and index SNP associations in or near SCN5A, SCN10A, CDKN1A, NFIA, HAND1, TBX5 and SETBP1 replicated in African Americans. In summary, rs3922844 was associated with QRS duration and SCN5A expression, two novel QRS loci were identified using transethnic meta-analysis, and a significant proportion of QRS-SNP associations discovered in populations of European descent were transferable to African Americans when adequate power was achieved.

KW - African Americans/genetics

KW - Alleles

KW - Cardiovascular Diseases/genetics

KW - Electrocardiography

KW - European Continental Ancestry Group/genetics

KW - Female

KW - Genome-Wide Association Study

KW - Genotype

KW - Heart Ventricles/physiopathology

KW - Humans

KW - Male

KW - Myocardium/pathology

KW - NAV1.5 Voltage-Gated Sodium Channel/genetics

KW - Polymorphism, Single Nucleotide/genetics

U2 - 10.1093/hmg/ddw284

DO - 10.1093/hmg/ddw284

M3 - SCORING: Journal article

C2 - 27577874

VL - 25

SP - 4350

EP - 4368

JO - HUM MOL GENET

JF - HUM MOL GENET

SN - 0964-6906

IS - 19

ER -