Discovery and refinement of loci associated with lipid levels

Cristen J Willer; Ellen M Schmidt; Sebanti Sengupta; Gina M Peloso; Stefan Gustafsson; Stavroula Kanoni; Andrea Ganna; Jin Chen; Martin L Buchkovich; Samia Mora; Jacques S Beckmann; Jennifer L Bragg-Gresham; Hsing-Yi Chang; Ayse Demirkan; Heleen M Den Hertog; Ron Do; Louise A Donnelly; Georg B Ehret; Tõnu Esko; Mary F Feitosa; Teresa Ferreira; Krista Fischer; Pierre Fontanillas; Ross M Fraser; Daniel F Freitag; Deepti Gurdasani; Kauko Heikkilä; Elina Hyppönen; Aaron Isaacs; Anne U Jackson; Åsa Johansson; Toby Johnson; Marika Kaakinen; Johannes Kettunen; Marcus E Kleber; Xiaohui Li; Jian'an Luan; Leo-Pekka Lyytikäinen; Patrik K E Magnusson; Massimo Mangino; Evelin Mihailov; May E Montasser; Martina Müller-Nurasyid; Ilja M Nolte; Jeffrey R O'Connell; Cameron D Palmer; Markus Perola; Ann-Kristin Petersen; Andrew Wong; Bruce H R Wolffenbuttel; Global Lipids Genetics Consortium

doi:10.1038/ng.2797

Discovery and refinement of loci associated with lipid levels

Cristen J Willer^*, Ellen M Schmidt, Sebanti Sengupta, Gina M Peloso, Stefan Gustafsson, Stavroula Kanoni, Andrea Ganna, Jin Chen, Martin L Buchkovich, Samia Mora, Jacques S Beckmann, Jennifer L Bragg-Gresham, Hsing-Yi Chang, Ayse Demirkan, Heleen M Den Hertog, Ron Do, Louise A Donnelly, Georg B Ehret, Tõnu Esko, Mary F FeitosaTeresa Ferreira, Krista Fischer, Pierre Fontanillas, Ross M Fraser, Daniel F Freitag, Deepti Gurdasani, Kauko Heikkilä, Elina Hyppönen, Aaron Isaacs, Anne U Jackson, Åsa Johansson, Toby Johnson, Marika Kaakinen, Johannes Kettunen, Marcus E Kleber, Xiaohui Li, Jian'an Luan, Leo-Pekka Lyytikäinen, Patrik K E Magnusson, Massimo Mangino, Evelin Mihailov, May E Montasser, Martina Müller-Nurasyid, Ilja M Nolte, Jeffrey R O'Connell, Cameron D Palmer, Markus Perola, Ann-Kristin Petersen, Andrew Wong, Bruce H R Wolffenbuttel, Global Lipids Genetics Consortium

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 × 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.

Original language	English
Pages (from-to)	1274-1283
Number of pages	10
Journal	Nature Genetics
Volume	45
Issue number	11
DOIs	https://doi.org/10.1038/ng.2797
Publication status	Published - Nov 2013
Externally published	Yes

Keywords

African Continental Ancestry Group/genetics
Asian Continental Ancestry Group/genetics
Cholesterol, HDL/blood
Cholesterol, LDL/blood
Coronary Artery Disease/blood
European Continental Ancestry Group/genetics
Genetic Predisposition to Disease
Genome-Wide Association Study
Genotype
Humans
Lipids/blood
Triglycerides/blood

Access to Document

10.1038/ng.2797Licence: Unspecified

Cite this

Willer, C. J., Schmidt, E. M., Sengupta, S., Peloso, G. M., Gustafsson, S., Kanoni, S., Ganna, A., Chen, J., Buchkovich, M. L., Mora, S., Beckmann, J. S., Bragg-Gresham, J. L., Chang, H.-Y., Demirkan, A., Den Hertog, H. M., Do, R., Donnelly, L. A., Ehret, G. B., Esko, T., ... Global Lipids Genetics Consortium (2013). Discovery and refinement of loci associated with lipid levels. Nature Genetics, 45(11), 1274-1283. https://doi.org/10.1038/ng.2797

@article{f1357920d8784b1bba52a896f8f7afd9,

title = "Discovery and refinement of loci associated with lipid levels",

abstract = "Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 × 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.",

keywords = "African Continental Ancestry Group/genetics, Asian Continental Ancestry Group/genetics, Cholesterol, HDL/blood, Cholesterol, LDL/blood, Coronary Artery Disease/blood, European Continental Ancestry Group/genetics, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Lipids/blood, Triglycerides/blood",

author = "Willer, {Cristen J} and Schmidt, {Ellen M} and Sebanti Sengupta and Peloso, {Gina M} and Stefan Gustafsson and Stavroula Kanoni and Andrea Ganna and Jin Chen and Buchkovich, {Martin L} and Samia Mora and Beckmann, {Jacques S} and Bragg-Gresham, {Jennifer L} and Hsing-Yi Chang and Ayse Demirkan and {Den Hertog}, {Heleen M} and Ron Do and Donnelly, {Louise A} and Ehret, {Georg B} and T{\~o}nu Esko and Feitosa, {Mary F} and Teresa Ferreira and Krista Fischer and Pierre Fontanillas and Fraser, {Ross M} and Freitag, {Daniel F} and Deepti Gurdasani and Kauko Heikkil{\"a} and Elina Hypp{\"o}nen and Aaron Isaacs and Jackson, {Anne U} and {\AA}sa Johansson and Toby Johnson and Marika Kaakinen and Johannes Kettunen and Kleber, {Marcus E} and Xiaohui Li and Jian'an Luan and Leo-Pekka Lyytik{\"a}inen and Magnusson, {Patrik K E} and Massimo Mangino and Evelin Mihailov and Montasser, {May E} and Martina M{\"u}ller-Nurasyid and Nolte, {Ilja M} and O'Connell, {Jeffrey R} and Palmer, {Cameron D} and Markus Perola and Ann-Kristin Petersen and Andrew Wong and Wolffenbuttel, {Bruce H R} and {Global Lipids Genetics Consortium}",

year = "2013",

month = nov,

doi = "10.1038/ng.2797",

language = "English",

volume = "45",

pages = "1274--1283",

journal = "Nature Genetics",

issn = "1061-4036",

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Willer, CJ, Schmidt, EM, Sengupta, S, Peloso, GM, Gustafsson, S, Kanoni, S, Ganna, A, Chen, J, Buchkovich, ML, Mora, S, Beckmann, JS, Bragg-Gresham, JL, Chang, H-Y, Demirkan, A, Den Hertog, HM, Do, R, Donnelly, LA, Ehret, GB, Esko, T, Feitosa, MF, Ferreira, T, Fischer, K, Fontanillas, P, Fraser, RM, Freitag, DF, Gurdasani, D, Heikkilä, K, Hyppönen, E, Isaacs, A, Jackson, AU, Johansson, Å, Johnson, T, Kaakinen, M, Kettunen, J, Kleber, ME, Li, X, Luan, J, Lyytikäinen, L-P, Magnusson, PKE, Mangino, M, Mihailov, E, Montasser, ME, Müller-Nurasyid, M, Nolte, IM, O'Connell, JR, Palmer, CD, Perola, M, Petersen, A-K, Wong, A, Wolffenbuttel, BHR & Global Lipids Genetics Consortium 2013, 'Discovery and refinement of loci associated with lipid levels', Nature Genetics, vol. 45, no. 11, pp. 1274-1283. https://doi.org/10.1038/ng.2797

TY - JOUR

T1 - Discovery and refinement of loci associated with lipid levels

AU - Willer, Cristen J

AU - Schmidt, Ellen M

AU - Sengupta, Sebanti

AU - Peloso, Gina M

AU - Gustafsson, Stefan

AU - Kanoni, Stavroula

AU - Ganna, Andrea

AU - Chen, Jin

AU - Buchkovich, Martin L

AU - Mora, Samia

AU - Beckmann, Jacques S

AU - Bragg-Gresham, Jennifer L

AU - Chang, Hsing-Yi

AU - Demirkan, Ayse

AU - Den Hertog, Heleen M

AU - Do, Ron

AU - Donnelly, Louise A

AU - Ehret, Georg B

AU - Esko, Tõnu

AU - Feitosa, Mary F

AU - Ferreira, Teresa

AU - Fischer, Krista

AU - Fontanillas, Pierre

AU - Fraser, Ross M

AU - Freitag, Daniel F

AU - Gurdasani, Deepti

AU - Heikkilä, Kauko

AU - Hyppönen, Elina

AU - Isaacs, Aaron

AU - Jackson, Anne U

AU - Johansson, Åsa

AU - Johnson, Toby

AU - Kaakinen, Marika

AU - Kettunen, Johannes

AU - Kleber, Marcus E

AU - Li, Xiaohui

AU - Luan, Jian'an

AU - Lyytikäinen, Leo-Pekka

AU - Magnusson, Patrik K E

AU - Mangino, Massimo

AU - Mihailov, Evelin

AU - Montasser, May E

AU - Müller-Nurasyid, Martina

AU - Nolte, Ilja M

AU - O'Connell, Jeffrey R

AU - Palmer, Cameron D

AU - Perola, Markus

AU - Petersen, Ann-Kristin

AU - Wong, Andrew

AU - Wolffenbuttel, Bruce H R

AU - Global Lipids Genetics Consortium

PY - 2013/11

Y1 - 2013/11

N2 - Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 × 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.

AB - Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 × 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.

KW - African Continental Ancestry Group/genetics

KW - Asian Continental Ancestry Group/genetics

KW - Cholesterol, HDL/blood

KW - Cholesterol, LDL/blood

KW - Coronary Artery Disease/blood

KW - European Continental Ancestry Group/genetics

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Genotype

KW - Humans

KW - Lipids/blood

KW - Triglycerides/blood

U2 - 10.1038/ng.2797

DO - 10.1038/ng.2797

M3 - Article

C2 - 24097068

SN - 1061-4036

VL - 45

SP - 1274

EP - 1283

JO - Nature Genetics

JF - Nature Genetics

IS - 11

ER -