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1. Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension

Author

Surendran, P., Drenos, F., Young, R., Warren, H., Cook, J.P., Manning, A.K., Grarup, N., Sim, X., Barnes, D.R., Witkowska, K., Staley, J.R., Tragante, V., Tukiainen, T., Yaghootkar, H., Masca, N., Freitag, D.F., Ferreira, T., Giannakopoulou, O., Tinker, A., Harakalova, M., Mihailov, E., Liu, C., Kraja, A.T., Nielsen, S.F., Rasheed, A., Samue, M., Zhao, W., Bonnycastle, L.L., Jackson, A.U., Narisu, N., Swift, A.J., Southam, L., Marten, J., Huyghe, J.R., Stancakova, A., Fava, C., Ohlsson, T., Matchan, A., Stirrups, K.E., Bork-Jensen, J., Gjesing, A.P., Kontto, J., Perola, M., Shaw-Hawkins, S., Havulinna, A.S., Zhang, H., Donnelly, L.A., Groves, C.J., Rayner, N.W., Neville, M.J., Robertson, N.R., Yiorkas, A.M., Herzig, K.H., Kajantie, E., Zhang, W., Willems, S.M., Lannfelt, L., Malerba, G., Soranzo, N., Trabetti, E., Verweij, N., Evangelou, E., Moayyeri, A., Vergnaud, A.C., Nelson, C.P., Poveda, A., Varga, T.V., Caslake, M., Craen, A.J.M. de, Trompet, S., Luan, J., Scott, R.A., Harris, S.E., Liewald, D.C.M., Marioni, R., Menni, C., Farmaki, A.E., Hallmans, G., Renstrom, F., Huffman, J.E., Hassinen, M., Burgess, S., Vasan, R.S., Felix, J.F., Uria-Nickelsen, M., Malarstign, A., Reilly, D.F., Hoek, M., Vogt, T.F., Lin, H.H., Lieb, W., Traylor, M., Markus, H.S., Highland, H.M., Justice, A.E., Marouli, E., Lindstrom, J., Uusitupa, M., Komulainen, P., Lakka, T.A., Rauramaa, R., Polasek, O., Rudan, I., Rolandsson, O., Franks, P.W., Dedoussis, G., Spector, T.D., Jousilahti, P., Mannisto, S., Deary, I.J., Starr, J.M., Langenberg, C., Wareham, N.J., Brown, M.J., Dominiczak, A.F., Connell, J.M., Jukema, J.W., Sattar, N., Ford, I., Packard, C.J., Esko, T., Magi, R., Metspalu, A., Boer, R.A. de, Meer, P. van der, Harst, P. van der, Gambaro, G., Ingelsson, E., Lind, L., Bakker, P.I.W. de, Numans, M.E., Brandslund, I., Christensen, C., Petersen, E.R.B., Korpi-Hyovalti, E., Oksa, H., Chambers, J.C., Kooner, J.S., Blakemore, A.I.F., Franks, S., Jarvelin, M.R., Husemoen, L.L., Linneberg, A., Skaaby, T., Thuesen, B., Karpe, F., Tuomilehto, J., Doney, A.S.F., Morris, A.D., Palmer, C.N.A., Holmen, O.L., Hveem, K., Willer, C.J., Tuomi, T., Groop, L., Karajamaki, A., Palotie, A., Ripatti, S., Salomaa, V., Alam, D.S., Majmnder, A.A.S., Angelantonio, E. di, Chowdhury, R., McCarthy, M.I., Poulter, N., Stanton, A.V., Sever, P., Amouyel, P., Arveiler, D., Blankenberg, S., Ferrieres, J., Kee, F., Kuulasmaa, K., Muller-Nurasyid, M., Veronesi, G., Virtamo, J., Deloukas, P., Elliott, P., Zeggini, E., Kathiresan, S., Melander, O., Kuusisto, J., Laakso, M., Padmanabhan, S., Porteous, D.J., Hayward, C., Scotland, G., Collins, F.S., Mohlke, K.L., Hansen, T., Pedersen, O., Boehnke, M., Stringham, H.M., Frossard, P., Newton-Cheh, C., Tobin, M.D., Nordestgaard, B.G., Caulfield, M.J., Mahajan, A., Morris, A.P., Tomaszewski, M., Samani, N.J., Saleheen, D., Asselbergs, F.W., Lindgren, C.M., Danesh, J., Wain, L.V., Butterworth, A.S., Howson, J.M.M., Munroe, P.B., CHARGE Heart Failure Consortiumm, EchoGen Consortiumm, Metastroke Consortiumm, Giant Consortiumm, EPIC-InterAct Consortium, Lifelines Cohort Study, Wellcome Trust Case Control Consor, Understanding Soc Sci Grp, EPIC-CVD Consortium, CHARGE Exome Chip Blood Pressure C, T2D-GENES Consortium, GoT2DGenes Consortium, ExomeBP Consortium, CHD Exome Consortium, Erasmus MC other, Epidemiology, Internal Medicine, Cardiovascular Centre (CVC), Restoring Organ Function by Means of Regenerative Medicine (REGENERATE), Surendran, Praveen [0000-0002-4911-6077], Barnes, Daniel [0000-0002-3781-7570], Marten, Jonathan [0000-0001-6916-2014], Johnson, Kathleen [0000-0002-6823-3252], Soranzo, Nicole [0000-0003-1095-3852], Luan, Jian'an [0000-0003-3137-6337], Burgess, Stephen [0000-0001-5365-8760], Traylor, Matthew [0000-0001-6624-8621], Markus, Hugh [0000-0002-9794-5996], Langenberg, Claudia [0000-0002-5017-7344], Wareham, Nicholas [0000-0003-1422-2993], Di Angelantonio, Emanuele [0000-0001-8776-6719], Chowdhury, Rajiv [0000-0003-4881-5690], Danesh, John [0000-0003-1158-6791], Butterworth, Adam [0000-0002-6915-9015], Howson, Joanna [0000-0001-7618-0050], Apollo - University of Cambridge Repository, British Heart Foundation, Home Office, Medical Research Council (MRC), Wellcome Trust, National Institute for Health Research, and Action on Hearing Loss

Subjects
0301 basic medicine, EchoGen Consortium, Population genetics, LOCI, Genome-wide association study, Blood Pressure, 030204 cardiovascular system & hematology, Bioinformatics, Genome-wide association studies, 0302 clinical medicine, Settore MED/14 - NEFROLOGIA, Missense mutation, GENE-CENTRIC ARRAY, GoT2DGenes Consortium, AGING RESEARCH, Genetics, education.field_of_study, CHD Exome+ Consortium, CHARGE-Heart Failure Consortium, 11 Medical And Health Sciences, 3. Good health, CARDIOVASCULAR-DISEASE, Hypertension, Medical genetics, HEART, Wellcome Trust Case Control Consortium, EPIC-InterAct Consortium, ExomeBP Consortium, CHARGE, Understanding Society Scientific Group, medicine.medical_specialty, Genotype, Population, Biology, CHARGE+ Exome Chip Blood Pressure Consortium, EPIC-CVD Consortium, Article, 03 medical and health sciences, Lifelines Cohort Study, genome-wide association studies, hypertension, population genetics, Genetic variation, GIANT Consortium, medicine, Journal Article, Humans, Genetic Predisposition to Disease, Allele, GENOME-WIDE ASSOCIATION, education, PLASMA-LEVELS, IDENTIFICATION, Genetic Variation, 06 Biological Sciences, medicine.disease, METASTROKE Consortium, T2D-GENES Consortium, 030104 developmental biology, Blood pressure, Pathophysiology of hypertension, RISK-FACTORS, Developmental Biology, Genome-Wide Association Study, blood pressure, gene
Abstract

High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used ~155,063 samples for independent replication. We identified 30 new blood pressure– or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention. N.P. has received financial support from several pharmaceutical companies that manufacture either blood pressure -lowering or lipid-lowering agents, or both, and consultancy fees. S.K. has received research grants from Merck, Bayer and Aegerion, is on the SAB of Catabasis, Regeneron Genetics Center, Merck and Celera, has equity in San Therapeutics and Catabasis, and performs consulting for Novartis, Aegerion, Bristol Myers Squibb, Sanofi, AstraZeneca and Alnylam. P. Sever has received research awards from Pfizer. A. Malarstig and M.U.-N. are full-time employees of Pfizer. D.F.R. and M. Hoek are full-time employees of Merck. M.J.C. is Chief Scientist for Genomics England, a UK government company. The authors declare no other competing financial interests.

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2. Publisher Correction: Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals.

Author

Surendran P, Feofanova EV, Lahrouchi N, Ntalla I, Karthikeyan S, Cook J, Chen L, Mifsud B, Yao C, Kraja AT, Cartwright JH, Hellwege JN, Giri A, Tragante V, Thorleifsson G, Liu DJ, Prins BP, Stewart ID, Cabrera CP, Eales JM, Akbarov A, Auer PL, Bielak LF, Bis JC, Braithwaite VS, Brody JA, Daw EW, Warren HR, Drenos F, Nielsen SF, Faul JD, Fauman EB, Fava C, Ferreira T, Foley CN, Franceschini N, Gao H, Giannakopoulou O, Giulianini F, Gudbjartsson DF, Guo X, Harris SE, Havulinna AS, Helgadottir A, Huffman JE, Hwang SJ, Kanoni S, Kontto J, Larson MG, Li-Gao R, Lindström J, Lotta LA, Lu Y, Luan J, Mahajan A, Malerba G, Masca NGD, Mei H, Menni C, Mook-Kanamori DO, Mosen-Ansorena D, Müller-Nurasyid M, Paré G, Paul DS, Perola M, Poveda A, Rauramaa R, Richard M, Richardson TG, Sepúlveda N, Sim X, Smith AV, Smith JA, Staley JR, Stanáková A, Sulem P, Thériault S, Thorsteinsdottir U, Trompet S, Varga TV, Velez Edwards DR, Veronesi G, Weiss S, Willems SM, Yao J, Young R, Yu B, Zhang W, Zhao JH, Zhao W, Zhao W, Evangelou E, Aeschbacher S, Asllanaj E, Blankenberg S, Bonnycastle LL, Bork-Jensen J, Brandslund I, Braund PS, Burgess S, Cho K, Christensen C, Connell J, Mutsert R, Dominiczak AF, Dörr M, Eiriksdottir G, Farmaki AE, Gaziano JM, Grarup N, Grove ML, Hallmans G, Hansen T, Have CT, Heiss G, Jørgensen ME, Jousilahti P, Kajantie E, Kamat M, Käräjämäki A, Karpe F, Koistinen HA, Kovesdy CP, Kuulasmaa K, Laatikainen T, Lannfelt L, Lee IT, Lee WJ, Linneberg A, Martin LW, Moitry M, Nadkarni G, Neville MJ, Palmer CNA, Papanicolaou GJ, Pedersen O, Peters J, Poulter N, Rasheed A, Rasmussen KL, Rayner NW, Mägi R, Renström F, Rettig R, Rossouw J, Schreiner PJ, Sever PS, Sigurdsson EL, Skaaby T, Sun YV, Sundstrom J, Thorgeirsson G, Esko T, Trabetti E, Tsao PS, Tuomi T, Turner ST, Tzoulaki I, Vaartjes I, Vergnaud AC, Willer CJ, Wilson PWF, Witte DR, Yonova-Doing E, Zhang H, Aliya N, Almgren P, Amouyel P, Asselbergs FW, Barnes MR, Blakemore AI, Boehnke M, Bots ML, Bottinger EP, Buring JE, Chambers JC, Chen YI, Chowdhury R, Conen D, Correa A, Davey Smith G, Boer RA, Deary IJ, Dedoussis G, Deloukas P, Di Angelantonio E, Elliott P, Felix SB, Ferrières J, Ford I, Fornage M, Franks PW, Franks S, Frossard P, Gambaro G, Gaunt TR, Groop L, Gudnason V, Harris TB, Hayward C, Hennig BJ, Herzig KH, Ingelsson E, Tuomilehto J, Järvelin MR, Jukema JW, Kardia SLR, Kee F, Kooner JS, Kooperberg C, Launer LJ, Lind L, Loos RJF, Majumder AAS, Laakso M, McCarthy MI, Melander O, Mohlke KL, Murray AD, Nordestgaard BG, Orho-Melander M, Packard CJ, Padmanabhan S, Palmas W, Polasek O, Porteous DJ, Prentice AM, Province MA, Relton CL, Rice K, Ridker PM, Rolandsson O, Rosendaal FR, Rotter JI, Rudan I, Salomaa V, Samani NJ, Sattar N, Sheu WH, Smith BH, Soranzo N, Spector TD, Starr JM, Sebert S, Taylor KD, Lakka TA, Timpson NJ, Tobin MD, van der Harst P, van der Meer P, Ramachandran VS, Verweij N, Virtamo J, Völker U, Weir DR, Zeggini E, Charchar FJ, Wareham NJ, Langenberg C, Tomaszewski M, Butterworth AS, Caulfield MJ, Danesh J, Edwards TL, Holm H, Hung AM, Lindgren CM, Liu C, Manning AK, Morris AP, Morrison AC, O'Donnell CJ, Psaty BM, Saleheen D, Stefansson K, Boerwinkle E, Chasman DI, Levy D, Newton-Cheh C, Munroe PB, and Howson JMM

Published
2021
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3. Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals.

Author

Surendran P, Feofanova EV, Lahrouchi N, Ntalla I, Karthikeyan S, Cook J, Chen L, Mifsud B, Yao C, Kraja AT, Cartwright JH, Hellwege JN, Giri A, Tragante V, Thorleifsson G, Liu DJ, Prins BP, Stewart ID, Cabrera CP, Eales JM, Akbarov A, Auer PL, Bielak LF, Bis JC, Braithwaite VS, Brody JA, Daw EW, Warren HR, Drenos F, Nielsen SF, Faul JD, Fauman EB, Fava C, Ferreira T, Foley CN, Franceschini N, Gao H, Giannakopoulou O, Giulianini F, Gudbjartsson DF, Guo X, Harris SE, Havulinna AS, Helgadottir A, Huffman JE, Hwang SJ, Kanoni S, Kontto J, Larson MG, Li-Gao R, Lindström J, Lotta LA, Lu Y, Luan J, Mahajan A, Malerba G, Masca NGD, Mei H, Menni C, Mook-Kanamori DO, Mosen-Ansorena D, Müller-Nurasyid M, Paré G, Paul DS, Perola M, Poveda A, Rauramaa R, Richard M, Richardson TG, Sepúlveda N, Sim X, Smith AV, Smith JA, Staley JR, Stanáková A, Sulem P, Thériault S, Thorsteinsdottir U, Trompet S, Varga TV, Velez Edwards DR, Veronesi G, Weiss S, Willems SM, Yao J, Young R, Yu B, Zhang W, Zhao JH, Zhao W, Zhao W, Evangelou E, Aeschbacher S, Asllanaj E, Blankenberg S, Bonnycastle LL, Bork-Jensen J, Brandslund I, Braund PS, Burgess S, Cho K, Christensen C, Connell J, Mutsert R, Dominiczak AF, Dörr M, Eiriksdottir G, Farmaki AE, Gaziano JM, Grarup N, Grove ML, Hallmans G, Hansen T, Have CT, Heiss G, Jørgensen ME, Jousilahti P, Kajantie E, Kamat M, Käräjämäki A, Karpe F, Koistinen HA, Kovesdy CP, Kuulasmaa K, Laatikainen T, Lannfelt L, Lee IT, Lee WJ, Linneberg A, Martin LW, Moitry M, Nadkarni G, Neville MJ, Palmer CNA, Papanicolaou GJ, Pedersen O, Peters J, Poulter N, Rasheed A, Rasmussen KL, Rayner NW, Mägi R, Renström F, Rettig R, Rossouw J, Schreiner PJ, Sever PS, Sigurdsson EL, Skaaby T, Sun YV, Sundstrom J, Thorgeirsson G, Esko T, Trabetti E, Tsao PS, Tuomi T, Turner ST, Tzoulaki I, Vaartjes I, Vergnaud AC, Willer CJ, Wilson PWF, Witte DR, Yonova-Doing E, Zhang H, Aliya N, Almgren P, Amouyel P, Asselbergs FW, Barnes MR, Blakemore AI, Boehnke M, Bots ML, Bottinger EP, Buring JE, Chambers JC, Chen YI, Chowdhury R, Conen D, Correa A, Davey Smith G, Boer RA, Deary IJ, Dedoussis G, Deloukas P, Di Angelantonio E, Elliott P, Felix SB, Ferrières J, Ford I, Fornage M, Franks PW, Franks S, Frossard P, Gambaro G, Gaunt TR, Groop L, Gudnason V, Harris TB, Hayward C, Hennig BJ, Herzig KH, Ingelsson E, Tuomilehto J, Järvelin MR, Jukema JW, Kardia SLR, Kee F, Kooner JS, Kooperberg C, Launer LJ, Lind L, Loos RJF, Majumder AAS, Laakso M, McCarthy MI, Melander O, Mohlke KL, Murray AD, Nordestgaard BG, Orho-Melander M, Packard CJ, Padmanabhan S, Palmas W, Polasek O, Porteous DJ, Prentice AM, Province MA, Relton CL, Rice K, Ridker PM, Rolandsson O, Rosendaal FR, Rotter JI, Rudan I, Salomaa V, Samani NJ, Sattar N, Sheu WH, Smith BH, Soranzo N, Spector TD, Starr JM, Sebert S, Taylor KD, Lakka TA, Timpson NJ, Tobin MD, van der Harst P, van der Meer P, Ramachandran VS, Verweij N, Virtamo J, Völker U, Weir DR, Zeggini E, Charchar FJ, Wareham NJ, Langenberg C, Tomaszewski M, Butterworth AS, Caulfield MJ, Danesh J, Edwards TL, Holm H, Hung AM, Lindgren CM, Liu C, Manning AK, Morris AP, Morrison AC, O'Donnell CJ, Psaty BM, Saleheen D, Stefansson K, Boerwinkle E, Chasman DI, Levy D, Newton-Cheh C, Munroe PB, and Howson JMM

Subjects
GATA5 Transcription Factor genetics, Genome-Wide Association Study, Genotype, Humans, Mutation genetics, Phospholipase C beta genetics, Polymorphism, Single Nucleotide genetics, Blood Pressure genetics, Gene Frequency genetics, Genetic Predisposition to Disease genetics, Hypertension genetics
Abstract

Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to ~1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency ≤ 0.01) variant BP associations (P < 5 × 10 -8 ), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were ~8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.

Published
2020
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4. Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension.

Author

Surendran P, Drenos F, Young R, Warren H, Cook JP, Manning AK, Grarup N, Sim X, Barnes DR, Witkowska K, Staley JR, Tragante V, Tukiainen T, Yaghootkar H, Masca N, Freitag DF, Ferreira T, Giannakopoulou O, Tinker A, Harakalova M, Mihailov E, Liu C, Kraja AT, Fallgaard Nielsen S, Rasheed A, Samuel M, Zhao W, Bonnycastle LL, Jackson AU, Narisu N, Swift AJ, Southam L, Marten J, Huyghe JR, Stančáková A, Fava C, Ohlsson T, Matchan A, Stirrups KE, Bork-Jensen J, Gjesing AP, Kontto J, Perola M, Shaw-Hawkins S, Havulinna AS, Zhang H, Donnelly LA, Groves CJ, Rayner NW, Neville MJ, Robertson NR, Yiorkas AM, Herzig KH, Kajantie E, Zhang W, Willems SM, Lannfelt L, Malerba G, Soranzo N, Trabetti E, Verweij N, Evangelou E, Moayyeri A, Vergnaud AC, Nelson CP, Poveda A, Varga TV, Caslake M, de Craen AJ, Trompet S, Luan J, Scott RA, Harris SE, Liewald DC, Marioni R, Menni C, Farmaki AE, Hallmans G, Renström F, Huffman JE, Hassinen M, Burgess S, Vasan RS, Felix JF, Uria-Nickelsen M, Malarstig A, Reily DF, Hoek M, Vogt T, Lin H, Lieb W, Traylor M, Markus HF, Highland HM, Justice AE, Marouli E, Lindström J, Uusitupa M, Komulainen P, Lakka TA, Rauramaa R, Polasek O, Rudan I, Rolandsson O, Franks PW, Dedoussis G, Spector TD, Jousilahti P, Männistö S, Deary IJ, Starr JM, Langenberg C, Wareham NJ, Brown MJ, Dominiczak AF, Connell JM, Jukema JW, Sattar N, Ford I, Packard CJ, Esko T, Mägi R, Metspalu A, de Boer RA, van der Meer P, van der Harst P, Gambaro G, Ingelsson E, Lind L, de Bakker PI, Numans ME, Brandslund I, Christensen C, Petersen ER, Korpi-Hyövälti E, Oksa H, Chambers JC, Kooner JS, Blakemore AI, Franks S, Jarvelin MR, Husemoen LL, Linneberg A, Skaaby T, Thuesen B, Karpe F, Tuomilehto J, Doney AS, Morris AD, Palmer CN, Holmen OL, Hveem K, Willer CJ, Tuomi T, Groop L, Käräjämäki A, Palotie A, Ripatti S, Salomaa V, Alam DS, Shafi Majumder AA, Di Angelantonio E, Chowdhury R, McCarthy MI, Poulter N, Stanton AV, Sever P, Amouyel P, Arveiler D, Blankenberg S, Ferrières J, Kee F, Kuulasmaa K, Müller-Nurasyid M, Veronesi G, Virtamo J, Deloukas P, Elliott P, Zeggini E, Kathiresan S, Melander O, Kuusisto J, Laakso M, Padmanabhan S, Porteous D, Hayward C, Scotland G, Collins FS, Mohlke KL, Hansen T, Pedersen O, Boehnke M, Stringham HM, Frossard P, Newton-Cheh C, Tobin MD, Nordestgaard BG, Caulfield MJ, Mahajan A, Morris AP, Tomaszewski M, Samani NJ, Saleheen D, Asselbergs FW, Lindgren CM, Danesh J, Wain LV, Butterworth AS, Howson JM, and Munroe PB

Subjects
Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Blood Pressure genetics, Genetic Variation, Hypertension genetics
Abstract

High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used ∼155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention., Competing Interests: Conflict of interests N. P. has received financial support from several pharmaceutical companies that manufacture either blood pressure lowering or lipid lowering agents, or both, and consultancy fees. S. K. has received Research Grant-Merck, Bayer, Aegerion; SAB-Catabasis, Regeneron Genetics Center, Merck, Celera; Equity-San Therapeutics, Catabasis; Consulting-Novartis, Aegerion, Bristol Myers-Squibb, Sanofi, AstraZeneca, Alnylam. P. Sever has received research awards from Pfizer Inc. A. Malarstig and M. Uria-Nickelsen are full time employees of Pfizer. D. Reily and M. Hoek are full time employees of Merck and co Inc. M.J. Caulfield is Chief Scientist for Genomics England a UK Government company. The authors declare no competing financial interest.

Published
2016
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