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Exome-wide association study of plasma lipids in >300,000 individuals

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Exome-wide association study of plasma lipids in >300,000 individuals. / Liu, Dajiang J; Peloso, Gina M; Yu, Haojie; Butterworth, Adam S; Wang, Xiao; Mahajan, Anubha; Saleheen, Danish; Emdin, Connor; Alam, Dewan; Alves, Alexessander Couto; Amouyel, Philippe; Di Angelantonio, Emanuele; Arveiler, Dominique; Assimes, Themistocles L; Auer, Paul L; Baber, Usman; Ballantyne, Christie M; Bang, Lia E; Benn, Marianne; Bis, Joshua C; Boehnke, Michael; Boerwinkle, Eric; Bork-Jensen, Jette; Bottinger, Erwin P; Brandslund, Ivan; Brown, Morris; Busonero, Fabio; Caulfield, Mark J; Chambers, John C; Chasman, Daniel I; Chen, Y Eugene; Chen, Yii-Der Ida; Chowdhury, Rajiv; Christensen, Cramer; Chu, Audrey Y; Connell, John M; Cucca, Francesco; Cupples, L Adrienne; Damrauer, Scott M; Davies, Gail; Deary, Ian J; Dedoussis, George; Denny, Joshua C; Dominiczak, Anna; Dubé, Marie-Pierre; Ebeling, Tapani; Eiriksdottir, Gudny; Esko, Tõnu; Small, Kerrin S; Spector, Timothy D; Charge Diabetes Working Group.

In: Nature Genetics, Vol. 49, No. 12, 12.2017, p. 1758-1766.

Research output: Contribution to journalLetter

Harvard

Liu, DJ, Peloso, GM, Yu, H, Butterworth, AS, Wang, X, Mahajan, A, Saleheen, D, Emdin, C, Alam, D, Alves, AC, Amouyel, P, Di Angelantonio, E, Arveiler, D, Assimes, TL, Auer, PL, Baber, U, Ballantyne, CM, Bang, LE, Benn, M, Bis, JC, Boehnke, M, Boerwinkle, E, Bork-Jensen, J, Bottinger, EP, Brandslund, I, Brown, M, Busonero, F, Caulfield, MJ, Chambers, JC, Chasman, DI, Chen, YE, Chen, Y-DI, Chowdhury, R, Christensen, C, Chu, AY, Connell, JM, Cucca, F, Cupples, LA, Damrauer, SM, Davies, G, Deary, IJ, Dedoussis, G, Denny, JC, Dominiczak, A, Dubé, M-P, Ebeling, T, Eiriksdottir, G, Esko, T, Small, KS, Spector, TD & Charge Diabetes Working Group 2017, 'Exome-wide association study of plasma lipids in >300,000 individuals', Nature Genetics, vol. 49, no. 12, pp. 1758-1766. https://doi.org/10.1038/ng.3977

APA

Liu, D. J., Peloso, G. M., Yu, H., Butterworth, A. S., Wang, X., Mahajan, A., ... Charge Diabetes Working Group (2017). Exome-wide association study of plasma lipids in >300,000 individuals. Nature Genetics, 49(12), 1758-1766. https://doi.org/10.1038/ng.3977

Vancouver

Liu DJ, Peloso GM, Yu H, Butterworth AS, Wang X, Mahajan A et al. Exome-wide association study of plasma lipids in >300,000 individuals. Nature Genetics. 2017 Dec;49(12):1758-1766. https://doi.org/10.1038/ng.3977

Author

Liu, Dajiang J ; Peloso, Gina M ; Yu, Haojie ; Butterworth, Adam S ; Wang, Xiao ; Mahajan, Anubha ; Saleheen, Danish ; Emdin, Connor ; Alam, Dewan ; Alves, Alexessander Couto ; Amouyel, Philippe ; Di Angelantonio, Emanuele ; Arveiler, Dominique ; Assimes, Themistocles L ; Auer, Paul L ; Baber, Usman ; Ballantyne, Christie M ; Bang, Lia E ; Benn, Marianne ; Bis, Joshua C ; Boehnke, Michael ; Boerwinkle, Eric ; Bork-Jensen, Jette ; Bottinger, Erwin P ; Brandslund, Ivan ; Brown, Morris ; Busonero, Fabio ; Caulfield, Mark J ; Chambers, John C ; Chasman, Daniel I ; Chen, Y Eugene ; Chen, Yii-Der Ida ; Chowdhury, Rajiv ; Christensen, Cramer ; Chu, Audrey Y ; Connell, John M ; Cucca, Francesco ; Cupples, L Adrienne ; Damrauer, Scott M ; Davies, Gail ; Deary, Ian J ; Dedoussis, George ; Denny, Joshua C ; Dominiczak, Anna ; Dubé, Marie-Pierre ; Ebeling, Tapani ; Eiriksdottir, Gudny ; Esko, Tõnu ; Small, Kerrin S ; Spector, Timothy D ; Charge Diabetes Working Group. / Exome-wide association study of plasma lipids in >300,000 individuals. In: Nature Genetics. 2017 ; Vol. 49, No. 12. pp. 1758-1766.

Bibtex Download

@article{ad901e67cb3342baa8f20f168d69ceac,
title = "Exome-wide association study of plasma lipids in >300,000 individuals",
abstract = "We screened variants on an exome-focused genotyping array in >300,000 participants (replication in >280,000 participants) and identified 444 independent variants in 250 loci significantly associated with total cholesterol (TC), high-density-lipoprotein cholesterol (HDL-C), low-density-lipoprotein cholesterol (LDL-C), and/or triglycerides (TG). At two loci (JAK2 and A1CF), experimental analysis in mice showed lipid changes consistent with the human data. We also found that: (i) beta-thalassemia trait carriers displayed lower TC and were protected from coronary artery disease (CAD); (ii) excluding the CETP locus, there was not a predictable relationship between plasma HDL-C and risk for age-related macular degeneration; (iii) only some mechanisms of lowering LDL-C appeared to increase risk for type 2 diabetes (T2D); and (iv) TG-lowering alleles involved in hepatic production of TG-rich lipoproteins (TM6SF2 and PNPLA3) tracked with higher liver fat, higher risk for T2D, and lower risk for CAD, whereas TG-lowering alleles involved in peripheral lipolysis (LPL and ANGPTL4) had no effect on liver fat but decreased risks for both T2D and CAD.",
keywords = "Journal Article",
author = "Liu, {Dajiang J} and Peloso, {Gina M} and Haojie Yu and Butterworth, {Adam S} and Xiao Wang and Anubha Mahajan and Danish Saleheen and Connor Emdin and Dewan Alam and Alves, {Alexessander Couto} and Philippe Amouyel and {Di Angelantonio}, Emanuele and Dominique Arveiler and Assimes, {Themistocles L} and Auer, {Paul L} and Usman Baber and Ballantyne, {Christie M} and Bang, {Lia E} and Marianne Benn and Bis, {Joshua C} and Michael Boehnke and Eric Boerwinkle and Jette Bork-Jensen and Bottinger, {Erwin P} and Ivan Brandslund and Morris Brown and Fabio Busonero and Caulfield, {Mark J} and Chambers, {John C} and Chasman, {Daniel I} and Chen, {Y Eugene} and Chen, {Yii-Der Ida} and Rajiv Chowdhury and Cramer Christensen and Chu, {Audrey Y} and Connell, {John M} and Francesco Cucca and Cupples, {L Adrienne} and Damrauer, {Scott M} and Gail Davies and Deary, {Ian J} and George Dedoussis and Denny, {Joshua C} and Anna Dominiczak and Marie-Pierre Dub{\'e} and Tapani Ebeling and Gudny Eiriksdottir and T{\~o}nu Esko and Small, {Kerrin S} and Spector, {Timothy D} and {Charge Diabetes Working Group}",
year = "2017",
month = "12",
doi = "10.1038/ng.3977",
language = "English",
volume = "49",
pages = "1758--1766",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. SN -",
number = "12",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - Exome-wide association study of plasma lipids in >300,000 individuals

AU - Liu, Dajiang J

AU - Peloso, Gina M

AU - Yu, Haojie

AU - Butterworth, Adam S

AU - Wang, Xiao

AU - Mahajan, Anubha

AU - Saleheen, Danish

AU - Emdin, Connor

AU - Alam, Dewan

AU - Alves, Alexessander Couto

AU - Amouyel, Philippe

AU - Di Angelantonio, Emanuele

AU - Arveiler, Dominique

AU - Assimes, Themistocles L

AU - Auer, Paul L

AU - Baber, Usman

AU - Ballantyne, Christie M

AU - Bang, Lia E

AU - Benn, Marianne

AU - Bis, Joshua C

AU - Boehnke, Michael

AU - Boerwinkle, Eric

AU - Bork-Jensen, Jette

AU - Bottinger, Erwin P

AU - Brandslund, Ivan

AU - Brown, Morris

AU - Busonero, Fabio

AU - Caulfield, Mark J

AU - Chambers, John C

AU - Chasman, Daniel I

AU - Chen, Y Eugene

AU - Chen, Yii-Der Ida

AU - Chowdhury, Rajiv

AU - Christensen, Cramer

AU - Chu, Audrey Y

AU - Connell, John M

AU - Cucca, Francesco

AU - Cupples, L Adrienne

AU - Damrauer, Scott M

AU - Davies, Gail

AU - Deary, Ian J

AU - Dedoussis, George

AU - Denny, Joshua C

AU - Dominiczak, Anna

AU - Dubé, Marie-Pierre

AU - Ebeling, Tapani

AU - Eiriksdottir, Gudny

AU - Esko, Tõnu

AU - Small, Kerrin S

AU - Spector, Timothy D

AU - Charge Diabetes Working Group

PY - 2017/12

Y1 - 2017/12

N2 - We screened variants on an exome-focused genotyping array in >300,000 participants (replication in >280,000 participants) and identified 444 independent variants in 250 loci significantly associated with total cholesterol (TC), high-density-lipoprotein cholesterol (HDL-C), low-density-lipoprotein cholesterol (LDL-C), and/or triglycerides (TG). At two loci (JAK2 and A1CF), experimental analysis in mice showed lipid changes consistent with the human data. We also found that: (i) beta-thalassemia trait carriers displayed lower TC and were protected from coronary artery disease (CAD); (ii) excluding the CETP locus, there was not a predictable relationship between plasma HDL-C and risk for age-related macular degeneration; (iii) only some mechanisms of lowering LDL-C appeared to increase risk for type 2 diabetes (T2D); and (iv) TG-lowering alleles involved in hepatic production of TG-rich lipoproteins (TM6SF2 and PNPLA3) tracked with higher liver fat, higher risk for T2D, and lower risk for CAD, whereas TG-lowering alleles involved in peripheral lipolysis (LPL and ANGPTL4) had no effect on liver fat but decreased risks for both T2D and CAD.

AB - We screened variants on an exome-focused genotyping array in >300,000 participants (replication in >280,000 participants) and identified 444 independent variants in 250 loci significantly associated with total cholesterol (TC), high-density-lipoprotein cholesterol (HDL-C), low-density-lipoprotein cholesterol (LDL-C), and/or triglycerides (TG). At two loci (JAK2 and A1CF), experimental analysis in mice showed lipid changes consistent with the human data. We also found that: (i) beta-thalassemia trait carriers displayed lower TC and were protected from coronary artery disease (CAD); (ii) excluding the CETP locus, there was not a predictable relationship between plasma HDL-C and risk for age-related macular degeneration; (iii) only some mechanisms of lowering LDL-C appeared to increase risk for type 2 diabetes (T2D); and (iv) TG-lowering alleles involved in hepatic production of TG-rich lipoproteins (TM6SF2 and PNPLA3) tracked with higher liver fat, higher risk for T2D, and lower risk for CAD, whereas TG-lowering alleles involved in peripheral lipolysis (LPL and ANGPTL4) had no effect on liver fat but decreased risks for both T2D and CAD.

KW - Journal Article

U2 - 10.1038/ng.3977

DO - 10.1038/ng.3977

M3 - Letter

C2 - 29083408

VL - 49

SP - 1758

EP - 1766

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 12

ER -

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