Integrating genetic, transcriptional, and functional analyses to identify 5 novel genes for atrial fibrillation

Circulation

Volumn 130, Issue 15, 2014, Pages 1225-1235

  Sinner, Moritz F ^b   Tucker, Nathan R ^a,f   Lunetta, Kathryn L ^c,d   Ozaki, Kouichi ^e   Smith, J Gustav ^f,g   Trompet, Stella ^h   Bis, Joshua C ⁱ   Lin, Honghuang ^d,j   Chung, Mina K ^k   Nielsen, Jonas B ^l,m   Lubitz, Steven A ^a   Krijthe, Bouwe P ^n,o   Magnani, Jared W ^d,j   Ye, Jiangchuan ^a   Gollob, Michael H ^p   Tsunoda, Tatsuhiko ^e   Müller Nurasyid, Martina ^b,q,r   Lichtner, Peter ^q   Peters, Annette ^q,s   Dolmatova, Elena ^a   Kubo, Michiaki ^e   Smith, Jonathan D ^k   Psaty, Bruce M ^i,t   Smith, Nicholas L ^i,t,u   Jukema, J Wouter ^h   Chasman, Daniel I ^v   Albert, Christine M ^v   Ebana, Yusuke ^w   Furukawa, Tetsushi ^w   Macfarlane, Peter W ^x   Harris, Tamara B ^y   Darbar, Dawood ^z   Dörr, Marcus ^aa   Holst, Anders G ^l,m   Svendsen, Jesper H ^l,m   Hofman, Albert ^n,o   Uitterlinden, Andre G ^n,o   Gudnason, Vilmundur ^ab,ac   Isobe, Mitsuaki ^w   Malik, Rainer ^b   Dichgans, Martin ^b,ad   Rosand, Jonathan ^a,f   Van Wagoner, David R ^k   Benjamin, Emelia J ^c,d,j   Milan, David J ^a   Melander, Olle ^g   Heckbert, Susan R ^i,t   Ford, Ian ^x   Liu, Yongmei ^ae   Barnard, John ^k   Olesen, Morten S ^l,m   Stricker, Bruno H C ^n,o,af   Tanaka, Toshihiro ^w   Kääb, Stefan ^b,s   Ellinor, Patrick T ^a,f   more..

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

^b LUDWIG MAXIMILIANS UNIVERSITY   (Germany)

^c BOSTON UNIVERSITY SCHOOL OF PUBLIC HEALTH   (United States)

^d FRAMINGHAM HEART STUDY   (United States)

^e RIKEN Center for Integrative Medical Sciences   (Japan)

^f MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

^g LUND UNIVERSITY   (Sweden)

^h LEIDEN UNIVERSITY MEDICAL CENTER   (Netherlands)

ⁱ UNIVERSITY OF WASHINGTON   (United States)

^j BOSTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^k LERNER RESEARCH INSTITUTE   (United States)

^l DANISH NATIONAL RESEARCH FOUNDATION   (Denmark)

^m UNIVERSITY OF COPENHAGEN   (Denmark)

ⁿ ERASMUS MEDICAL CENTER   (Netherlands)

^o Netherlands Consortium for Healthy Ageing   (Netherlands)

^p UNIVERSITY OF OTTAWA HEART INSTITUTE   (Canada)

^q INSTITUTE OF EPIDEMIOLOGY   (Germany)

^r UNIVERSITY OF MUNICH   (Germany)

^s Deutsches Zentrum Für Herz Kreislaufforschung E V   (Germany)

^t CENTER FOR HEALTH STUDIES   (United States)

^u DEPARTMENT OF VETERANS AFFAIRS   (United States)

^v HARVARD MEDICAL SCHOOL   (United States)

^w TOKYO MEDICAL AND DENTAL UNIVERSITY   (Japan)

^x UNIVERSITY OF GLASGOW   (United Kingdom)

^y NATIONAL INSTITUTE ON AGING   (United States)

^z VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^aa UNIVERSITY OF GREIFSWALD   (Germany)

^ab ICELANDIC HEART ASSOCIATION   (Iceland)

^ac UNIVERSITY OF ICELAND   (Iceland)

^ad Germany 3 Munich Cluster for Systems Neurology   (Germany)

^ae WAKE FOREST SCHOOL OF MEDICINE   (United States)

^af Inspectorate for Health Care   (Netherlands)

more..

Author keywords

Atrial fibrillation; Epidemiology; Gene expression; Genetics; Polymorphism; Single nucleotide; Zebrafish

Indexed keywords

TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR CUX2; TRANSCRIPTION FACTOR TBX5; UBIQUITIN PROTEIN LIGASE E3; UNCLASSIFIED DRUG; CAND2 PROTEIN, ZEBRAFISH; CONNEXIN 43; CUX1 PROTEIN, HUMAN; GJA1 PROTEIN, HUMAN; HOMEODOMAIN PROTEIN; MUSCLE PROTEIN; NEURL1 PROTEIN, HUMAN; NEURL1 PROTEIN, ZEBRAFISH; NUCLEAR PROTEIN; REPRESSOR PROTEIN; T BOX TRANSCRIPTION FACTOR; T-BOX TRANSCRIPTION FACTOR 5; TIP120B PROTEIN, HUMAN; TRANSCRIPTION FACTOR PITX2; UBIQUITIN PROTEIN LIGASE; ZEBRAFISH PROTEIN;

ACTION POTENTIAL DURATION; ADULT; ANIMAL TISSUE; ARTICLE; CAND2 GENE; CARDIOVASCULAR RISK; CEREBROVASCULAR ACCIDENT; CONTROLLED STUDY; CUX2 GENE; EUROPEAN; FEMALE; GENE; GENE EXPRESSION; GENE INTERACTION; GENE MAPPING; GENE SILENCING; GENETIC TRANSCRIPTION; GENOTYPE; GJA1 GENE; HEART ATRIUM FIBRILLATION; HUMAN; HUMAN TISSUE; JAPANESE (PEOPLE); MAJOR CLINICAL STUDY; MALE; META ANALYSIS (TOPIC); NEURL GENE; NONHUMAN; ORTHOLOGY; PRIORITY JOURNAL; QUANTITATIVE TRAIT LOCUS; SINGLE NUCLEOTIDE POLYMORPHISM; TBX5 GENE; ZEBRA FISH; AGED; ANIMAL; ATRIAL FIBRILLATION; CHROMOSOME MAP; COMPARATIVE STUDY; ETHNOLOGY; EUROPE; GENE LOCUS; GENETIC PREDISPOSITION; GENETICS; JAPAN; META ANALYSIS; MIDDLE AGED; PATHOPHYSIOLOGY; PHYSIOLOGY;

AGED; ANIMALS; ATRIAL FIBRILLATION; CHROMOSOME MAPPING; CONNEXIN 43; EUROPE; FEMALE; GENE KNOCKDOWN TECHNIQUES; GENETIC LOCI; GENETIC PREDISPOSITION TO DISEASE; GENOTYPE; HOMEODOMAIN PROTEINS; HUMANS; JAPAN; MALE; MIDDLE AGED; MUSCLE PROTEINS; NUCLEAR PROTEINS; QUANTITATIVE TRAIT LOCI; REPRESSOR PROTEINS; T-BOX DOMAIN PROTEINS; TRANSCRIPTION FACTORS; UBIQUITIN-PROTEIN LIGASES; ZEBRAFISH; ZEBRAFISH PROTEINS;

EID: 84922637956     PISSN: 00097322     EISSN: 15244539     Source Type: Journal    
DOI: 10.1161/CIRCULATIONAHA.114.009892     Document Type: Article

References (28)

1. Wann LS, Curtis AB, January CT, Ellenbogen KA, Lowe JE, Estes NA 3rd, Page RL, Ezekowitz MD, Slotwiner DJ, Jackman WM, Stevenson WG, Tracy CM, Fuster V, Rydén LE, Cannom DS, Le Heuzey JY, Crijns HJ, Lowe JE, Curtis AB, Olsson S, Ellenbogen KA, Prystowsky EN, Halperin JL, Tamargo JL, Kay GN, Wann LS, Jacobs AK, Anderson JL, Albert N, Hochman JS, Buller CE, Kushner FG, Creager MA, Ohman EM, Ettinger SM, Stevenson WG, Guyton RA, Tarkington LG, Halperin JL, Yancy CW; 2006 Writing Committee Members; ACCF/AHA Task Force Members. 2011 ACCF/AHA/HRS focused update on the management of patients with atrial fibrillation (updating the 2006 guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Heart Rhythm. 2011;8:157-176.
2. Benjamin EJ, Levy D, Vaziri SM, D'Agostino RB, Belanger AJ, Wolf PA. Independent risk factors for atrial fibrillation in a population-based cohort: the Framingham Heart Study. JAMA. 1994;271:840-844.
3. Lubitz SA, Yin X, Fontes JD, Magnani JW, Rienstra M, Pai M, Villalon ML, Vasan RS, Pencina MJ, Levy D, Larson MG, Ellinor PT, Benjamin EJ. Association between familial atrial fibrillation and risk of new-onset atrial fibrillation. JAMA. 2010;304:2263-2269.
4. Ellinor PT, Lunetta KL, Albert CM, Glazer NL, Ritchie MD, Smith AV, Arking DE, Müller-Nurasyid M, Krijthe BP, Lubitz SA, Bis JC, Chung MK, Dörr M, Ozaki K, Roberts JD, Smith JG, Pfeufer A, Sinner MF, Lohman K, Ding J, Smith NL, Smith JD, Rienstra M, Rice KM, Van Wagoner DR, Magnani JW, Wakili R, Clauss S, Rotter JI, Steinbeck G, Launer LJ, Davies RW, Borkovich M, Harris TB, Lin H, Völker U, Völzke H, Milan DJ, Hofman A, Boerwinkle E, Chen LY, Soliman EZ, Voight BF, Li G, Chakravarti A, Kubo M, Tedrow UB, Rose LM, Ridker PM, Conen D, Tsunoda T, Furukawa T, Sotoodehnia N, Xu S, Kamatani N, Levy D, Nakamura Y, Parvez B, Mahida S, Furie KL, Rosand J, Muhammad R, Psaty BM, Meitinger T, Perz S, Wichmann HE, Witteman JC, Kao WH, Kathiresan S, Roden DM, Uitterlinden AG, Rivadeneira F, McKnight B, Sjögren M, Newman AB, Liu Y, Gollob MH, Melander O, Tanaka T, Stricker BH, Felix SB, Alonso A, Darbar D, Barnard J, Chasman DI, Heckbert SR, Benjamin EJ, Gudnason V, Kääb S. Meta-analysis identifies six new susceptibility loci for atrial fibrillation. Nat Genet. 2012;44:670-675.
5. Raychaudhuri S, Plenge RM, Rossin EJ, Ng AC, Purcell SM, Sklar P, Scolnick EM, Xavier RJ, Altshuler D, Daly MJ; International Schizophrenia Consortium. Identifying relationships among genomic disease regions: predicting genes at pathogenic SNP associations and rare deletions. PLoS Genet. 2009;5:e1000534.
6. Milan DJ, Kim AM, Winterfield JR, Jones IL, Pfeufer A, Sanna S, Arking DE, Amsterdam AH, Sabeh KM, Mably JD, Rosenbaum DS, Peterson RT, Chakravarti A, Kääb S, Roden DM, MacRae CA. Drug-sensitized zebrafish screen identifies multiple genes, including GINS3, as regulators of myocardial repolarization. Circulation. 2009;120:553-559.
7. Pavlopoulos E, Trifilieff P, Chevaleyre V, Fioriti L, Zairis S, Pagano A, Malleret G, Kandel ER. Neuralized1 activates CPEB3: a function for nonproteolytic ubiquitin in synaptic plasticity and memory storage. Cell. 2011;147:1369-1383.
8. Zou W, Chen X, Shim JH, Huang Z, Brady N, Hu D, Drapp R, Sigrist K, Glimcher LH, Jones D. The E3 ubiquitin ligase Wwp2 regulates craniofacial development through mono-ubiquitylation of Goosecoid. Nat Cell Biol. 2011;13:59-65.
9. Traylor M, Farrall M, Holliday EG, Sudlow C, Hopewell JC, Cheng YC, Fornage M, Ikram MA, Malik R, Bevan S, Thorsteinsdottir U, Nalls MA, Longstreth W, Wiggins KL, Yadav S, Parati EA, Destefano AL, Worrall BB, Kittner SJ, Khan MS, Reiner AP, Helgadottir A, Achterberg S, Fernandez-Cadenas I, Abboud S, Schmidt R, Walters M, Chen WM, Ringelstein EB, O'Donnell M, Ho WK, Pera J, Lemmens R, Norrving B, Higgins P, Benn M, Sale M, Kuhlenbäumer G, Doney AS, Vicente AM, Delavaran H, Algra A, Davies G, Oliveira SA, Palmer CN, Deary I, Schmidt H, Pandolfo M, Montaner J, Carty C, de Bakker PI, Kostulas K, Ferro JM, van Zuydam NR, Valdimarsson E, Nordestgaard BG, Lindgren A, Thijs V, Slowik A, Saleheen D, Paré G, Berger K, Thorleifsson G, Hofman A, Mosley TH, Mitchell BD, Furie K, Clarke R, Levi C, Seshadri S, Gschwendtner A, Boncoraglio GB, Sharma P, Bis JC, Gretarsdottir S, Psaty BM, Rothwell PM, Rosand J, Meschia JF, Stefansson K, Dichgans M, Markus HS; Australian Stroke Genetics Collaborative, Wellcome Trust Case Control Consortium 2 (WTCCC2); International Stroke Genetics Consortium. Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE collaboration): a meta-analysis of genome-wide association studies. Lancet Neurol. 2012;11:951-962.
10. Timmusk T, Palm K, Belluardo N, Mudò G, Neuman T. Dendritic localization of mammalian neuralized mRNA encoding a protein with transcription repression activities. Mol Cell Neurosci. 2002;20:649-668.
11. Nattel S. New ideas about atrial fibrillation 50 years on. Nature. 2002;415: 219-226.
12. Wakili R, Voigt N, Kääb S, Dobrev D, Nattel S. Recent advances in the molecular pathophysiology of atrial fibrillation. J Clin Invest. 2011;121:2955-2968.
13. Bikou O, Thomas D, Trappe K, Lugenbiel P, Kelemen K, Koch M, Soucek R, Voss F, Becker R, Katus HA, Bauer A. Connexin 43 gene therapy prevents persistent atrial fibrillation in a porcine model. Cardiovasc Res. 2011;92:218-225.
14. Mommersteeg MT, Brown NA, Prall OW, de Gier-de Vries C, Harvey RP, Moorman AF, Christoffels VM. Pitx2c and Nkx2-5 are required for the formation and identity of the pulmonary myocardium. Circ Res. 2007;101:902-909.
15. Moskowitz IP, Kim JB, Moore ML, Wolf CM, Peterson MA, Shendure J, Nobrega MA, Yokota Y, Berul C, Izumo S, Seidman JG, Seidman CE. A molecular pathway including Id2, Tbx5, and Nkx2-5 required for cardiac conduction system development. Cell. 2007;129:1365-1376.
16. Postma AV, van de Meerakker JB, Mathijssen IB, Barnett P, Christoffels VM, Ilgun A, Lam J, Wilde AA, Lekanne Deprez RH, Moorman AF. A gainof- function TBX5 mutation is associated with atypical Holt-Oram syndrome and paroxysmal atrial fibrillation. Circ Res. 2008;102:1433-1442.
17. Holm H, Gudbjartsson DF, Arnar DO, Thorleifsson G, Thorgeirsson G, Stefansdottir H, Gudjonsson SA, Jonasdottir A, Mathiesen EB, Njølstad I, Nyrnes A, Wilsgaard T, Hald EM, Hveem K, Stoltenberg C, Løchen ML, Kong A, Thorsteinsdottir U, Stefansson K. Several common variants modulate heart rate, PR interval and QRS duration. Nat Genet. 2010;42:117-122.
18. Pfeufer A, van Noord C, Marciante KD, Arking DE, Larson MG, Smith AV, Tarasov KV, Müller M, Sotoodehnia N, Sinner MF, Verwoert GC, Li M, Kao WH, Köttgen A, Coresh J, Bis JC, Psaty BM, Rice K, Rotter JI, Rivadeneira F, Hofman A, Kors JA, Stricker BH, Uitterlinden AG, van Duijn CM, Beckmann BM, Sauter W, Gieger C, Lubitz SA, Newton-Cheh C, Wang TJ, Magnani JW, Schnabel RB, Chung MK, Barnard J, Smith JD, Van Wagoner DR, Vasan RS, Aspelund T, Eiriksdottir G, Harris TB, Launer LJ, Najjar SS, Lakatta E, Schlessinger D, Uda M, Abecasis GR, Müller-Myhsok B, Ehret GB, Boerwinkle E, Chakravarti A, Soliman EZ, Lunetta KL, Perz S, Wichmann HE, Meitinger T, Levy D, Gudnason V, Ellinor PT, Sanna S, Kääb S, Witteman JC, Alonso A, Benjamin EJ, Heckbert SR. Genome-wide association study of PR interval. Nat Genet. 2010;42:153-159.
19. Aoki T, Okada N, Ishida M, Yogosawa S, Makino Y, Tamura TA. TIP120B: a novel TIP120-family protein that is expressed specifically in muscle tissues. Biochem Biophys Res Commun. 1999;261:911-916.
20. Li JY, Hou XE, Dahlström A. GAP-43 and its relation to autonomic and sensory neurons in sciatic nerve and gastrocnemius muscle in the rat. J Auton Nerv Syst. 1995;50:299-309.
21. Thibodeau IL, Xu J, Li Q, Liu G, Lam K, Veinot JP, Birnie DH, Jones DL, Krahn AD, Lemery R, Nicholson BJ, Gollob MH. Paradigm of genetic mosaicism and lone atrial fibrillation: physiological characterization of a connexin 43-deletion mutant identified from atrial tissue. Circulation. 2010;122:236-244.
22. Tuomi JM, Tyml K, Jones DL. Atrial tachycardia/fibrillation in the connexin 43 G60S mutant (Oculodentodigital dysplasia) mouse. Am J Physiol Heart Circ Physiol. 2011;300:H1402-H1411.
23. Eijgelsheim M, Newton-Cheh C, Sotoodehnia N, de Bakker PI, Müller M, Morrison AC, Smith AV, Isaacs A, Sanna S, Dörr M, Navarro P, Fuchsberger C, Nolte IM, de Geus EJ, Estrada K, Hwang SJ, Bis JC, Rückert IM, Alonso A, Launer LJ, Hottenga JJ, Rivadeneira F, Noseworthy PA, Rice KM, Perz S, Arking DE, Spector TD, Kors JA, Aulchenko YS, Tarasov KV, Homuth G, Wild SH, Marroni F, Gieger C, Licht CM, Prineas RJ, Hofman A, Rotter JI, Hicks AA, Ernst F, Najjar SS, Wright AF, Peters A, Fox ER, Oostra BA, Kroemer HK, Couper D, Völzke H, Campbell H, Meitinger T, Uda M, Witteman JC, Psaty BM, Wichmann HE, Harris TB, Kääb S, Siscovick DS, Jamshidi Y, Uitterlinden AG, Folsom AR, Larson MG, Wilson JF, Penninx BW, Snieder H, Pramstaller PP, van Duijn CM, Lakatta EG, Felix SB, Gudnason V, Pfeufer A, Heckbert SR, Stricker BH, Boerwinkle E, O'Donnell CJ. Genome-wide association analysis identifies multiple loci related to resting heart rate. Hum Mol Genet. 2010;19:3885-3894.
24. Iulianella A, Sharma M, Durnin M, Vanden Heuvel GB, Trainor PA. Cux2 (Cutl2) integrates neural progenitor development with cell-cycle progression during spinal cord neurogenesis. Development. 2008;135:729-741.
25. Huang J, Ellinghaus D, Franke A, Howie B, Li Y. 1000 Genomes-based imputation identifies novel and refined associations for the Wellcome Trust Case Control Consortium phase 1 data. Eur J Hum Genet. 2012;20:801-805.
26. Lee JY, Lee BS, Shin DJ, Woo Park K, Shin YA, Joong Kim K, Heo L, Young Lee J, Kyoung Kim Y, Jin Kim Y, Bum Hong C, Lee SH, Yoon D, Jung Ku H, Oh IY, Kim BJ, Lee J, Park SJ, Kim J, Kawk HK, Lee JE, Park HK, Lee JE, Nam HY, Park HY, Shin C, Yokota M, Asano H, Nakatochi M, Matsubara T, Kitajima H, Yamamoto K, Kim HL, Han BG, Cho MC, Jang Y, Kim HS, Euy Park J, Lee JY. A genome-wide association study of a coronary artery disease risk variant. J Hum Genet. 2013;58:120-126.
27. Gretarsdottir S, Thorleifsson G, Manolescu A, Styrkarsdottir U, Helgadottir A, Gschwendtner A, Kostulas K, Kuhlenbäumer G, Bevan S, Jonsdottir T, Bjarnason H, Saemundsdottir J, Palsson S, Arnar DO, Holm H, Thorgeirsson G, Valdimarsson EM, Sveinbjörnsdottir S, Gieger C, Berger K, Wichmann HE, Hillert J, Markus H, Gulcher JR, Ringelstein EB, Kong A, Dichgans M, Gudbjartsson DF, Thorsteinsdottir U, Stefansson K. Risk variants for atrial fibrillation on chromosome 4q25 associate with ischemic stroke. Ann Neurol. 2008;64:402-409.
28. Gudbjartsson DF, Holm H, Gretarsdottir S, Thorleifsson G, Walters GB, Thorgeirsson G, Gulcher J, Mathiesen EB, Njølstad I, Nyrnes A, Wilsgaard T, Hald EM, Hveem K, Stoltenberg C, Kucera G, Stubblefield T, Carter S, Roden D, Ng MC, Baum L, So WY, Wong KS, Chan JC, Gieger C, Wichmann HE, Gschwendtner A, Dichgans M, Kuhlenbäumer G, Berger K, Ringelstein EB, Bevan S, Markus HS, Kostulas K, Hillert J, Sveinbjörnsdóttir S, Valdimarsson EM, Løchen ML, Ma RC, Darbar D, Kong A, Arnar DO, Thorsteinsdottir U, Stefansson K. A sequence variant in ZFHX3 on 16q22 associates with atrial fibrillation and ischemic stroke. Nat Genet. 2009;41:876-878.