Evidence for a gene influencing fasting LDL cholesterol and triglyceride levels on chromosome 21q

Kari E. North; Michael B. Miller; Hilary Coon; Lisa J. Martin; James M. Peacock; Donna Arnett; Binbin Zhang; Michael Province; Albert Oberman; John Blangero; Laura Almasy; R. Curtis Ellison; Gerardo Heiss

doi:10.1016/j.atherosclerosis.2004.09.009

Evidence for a gene influencing fasting LDL cholesterol and triglyceride levels on chromosome 21q

Kari E. North, Michael B. Miller, Hilary Coon, Lisa J. Martin, James M. Peacock, Donna Arnett, Binbin Zhang, Michael Province, Albert Oberman, John Blangero, Laura Almasy, R. Curtis Ellison, Gerardo Heiss

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

18 Scopus citations

Abstract

High levels of low-density lipoprotein (LDL) cholesterol, low levels of high-density lipoprotein (HDL) cholesterol, and high levels of triglycerides (TG) are strong predictors of cardiovascular disease risk. Motivated by previous evidence for pleiotropy between cholesterol and TG levels, we conducted bivariate linkage analysis of LDL cholesterol and TG concentration among participants of the Hypertension Genetic Epidemiolgy Network (HyperGEN), one of four networks in the NHLBI sponsored Family Blood Pressure Program Project. All available hypertensive siblings and their first-degree relatives were recruited. Both phenotypes were similarly adjusted for ethnicity, study center, sex, age, age-by-sex interactions, smoking, alcohol consumption, hormone use, diabetes medication use, and waist circumference. Variance component linkage analysis was performed as implemented in SOLAR, using ethnicity-specific marker allele frequencies derived from founders and multipoint IBDs calculated in MERLIN. A maximum genome-wide empirical LOD score of 3.9 was detected on chromosome 21 at 54 cM, between markers D21S2055 and D21S1446. This signal overlaps with suggestive and/or significant linkages for total cholesterol, LDL cholesterol, and apolipoprotein B in three other studies and is suggestive of one or more genes on chromosome 21q jointly regulating LDL cholesterol and TG concentration.

Original language	English
Pages (from-to)	119-125
Number of pages	7
Journal	Atherosclerosis
Volume	179
Issue number	1
DOIs	https://doi.org/10.1016/j.atherosclerosis.2004.09.009
State	Published - Mar 2005

Bibliographical note

Funding Information:
We wish to first acknowledge the participants of the HyperGEN study. This hypertension network is funded by cooperative agreements (U10) with NHLBI: HL54471, HL54472, HL54473, HL54495, HL54496, HL54497, HL54509, HL54515. We also acknowledge the HyperGEN Participating Institutions and Principal Staff: Network Center/University of Utah Field Center: Steven C. Hunt, Roger R. Williams (deceased), Hilary Coon, Paul N. Hopkins, Janet Hood, Lily Wu, Jan Skuppin; University of Alabama at Birmingham Field Center: Albert Oberman, Cora E. Lewis, Michael T. Weaver, Phillip Johnson, Susan Walker, Christie Oden; Boston University/Framingham Field Center: R. Curtis Ellison, Richard H. Myers, Yuqing Zhang, Luc Djoussé, Jemma B. Wilk, Greta Lee Splansky; University of Minnesota Field Center: Donna Arnett, Aaron R. Folsom, Mike Miller, Jim Pankow, Gregory Feitl, Barb Lux; University of North Carolina Field Center: Gerardo Heiss, Barry I. Freedman, Kari North, Kathryn Rose, Amy Haire; Data Coordinating Center,Washington University: D.C. Rao, Michael A. Province, Ingrid B. Borecki, Avril Adelman, Derek Morgan, Karen Schwander, David Lehner, Aldi Kraja, Stephen Mandel; Central Biochemistry Lab, University of Minnesota: John H. Eckfeldt, Ronald C. McGlennen, Michael Y. Tsai, Catherine Leiendecker-Foster, Greg Rynders, Jean Bucksa; Molecular Genetics Laboratory, University of Utah: Mark Leppert, Steven C. Hunt, Jean-Marc Lalouel, Robert Weiss; National Heart, Lung, & Blood Institute: Susan E. Old, Millicent Higgins (retired), Cashell Jaquish, Martha Lundberg, Mariana Gerschenson. In addition, we acknowledge Brigitt Heier and Marilyn Knowles for assistance in the preparation of this manuscript. We also thank the University of Minnesota Supercomputing Institute for Digital Simulation and Advanced Computation for use of the IBM SP supercomputer.

Keywords

Cholesterol
Linkage (genetics)
Lipids
Triglycerides

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.atherosclerosis.2004.09.009

Cite this

@article{3ce76bae8ec4482ca1fc2596c2f8f05c,

title = "Evidence for a gene influencing fasting LDL cholesterol and triglyceride levels on chromosome 21q",

abstract = "High levels of low-density lipoprotein (LDL) cholesterol, low levels of high-density lipoprotein (HDL) cholesterol, and high levels of triglycerides (TG) are strong predictors of cardiovascular disease risk. Motivated by previous evidence for pleiotropy between cholesterol and TG levels, we conducted bivariate linkage analysis of LDL cholesterol and TG concentration among participants of the Hypertension Genetic Epidemiolgy Network (HyperGEN), one of four networks in the NHLBI sponsored Family Blood Pressure Program Project. All available hypertensive siblings and their first-degree relatives were recruited. Both phenotypes were similarly adjusted for ethnicity, study center, sex, age, age-by-sex interactions, smoking, alcohol consumption, hormone use, diabetes medication use, and waist circumference. Variance component linkage analysis was performed as implemented in SOLAR, using ethnicity-specific marker allele frequencies derived from founders and multipoint IBDs calculated in MERLIN. A maximum genome-wide empirical LOD score of 3.9 was detected on chromosome 21 at 54 cM, between markers D21S2055 and D21S1446. This signal overlaps with suggestive and/or significant linkages for total cholesterol, LDL cholesterol, and apolipoprotein B in three other studies and is suggestive of one or more genes on chromosome 21q jointly regulating LDL cholesterol and TG concentration.",

keywords = "Cholesterol, Linkage (genetics), Lipids, Triglycerides",

author = "North, {Kari E.} and Miller, {Michael B.} and Hilary Coon and Martin, {Lisa J.} and Peacock, {James M.} and Donna Arnett and Binbin Zhang and Michael Province and Albert Oberman and John Blangero and Laura Almasy and Ellison, {R. Curtis} and Gerardo Heiss",

note = "Funding Information: We wish to first acknowledge the participants of the HyperGEN study. This hypertension network is funded by cooperative agreements (U10) with NHLBI: HL54471, HL54472, HL54473, HL54495, HL54496, HL54497, HL54509, HL54515. We also acknowledge the HyperGEN Participating Institutions and Principal Staff: Network Center/University of Utah Field Center: Steven C. Hunt, Roger R. Williams (deceased), Hilary Coon, Paul N. Hopkins, Janet Hood, Lily Wu, Jan Skuppin; University of Alabama at Birmingham Field Center: Albert Oberman, Cora E. Lewis, Michael T. Weaver, Phillip Johnson, Susan Walker, Christie Oden; Boston University/Framingham Field Center: R. Curtis Ellison, Richard H. Myers, Yuqing Zhang, Luc Djouss{\'e}, Jemma B. Wilk, Greta Lee Splansky; University of Minnesota Field Center: Donna Arnett, Aaron R. Folsom, Mike Miller, Jim Pankow, Gregory Feitl, Barb Lux; University of North Carolina Field Center: Gerardo Heiss, Barry I. Freedman, Kari North, Kathryn Rose, Amy Haire; Data Coordinating Center,Washington University: D.C. Rao, Michael A. Province, Ingrid B. Borecki, Avril Adelman, Derek Morgan, Karen Schwander, David Lehner, Aldi Kraja, Stephen Mandel; Central Biochemistry Lab, University of Minnesota: John H. Eckfeldt, Ronald C. McGlennen, Michael Y. Tsai, Catherine Leiendecker-Foster, Greg Rynders, Jean Bucksa; Molecular Genetics Laboratory, University of Utah: Mark Leppert, Steven C. Hunt, Jean-Marc Lalouel, Robert Weiss; National Heart, Lung, & Blood Institute: Susan E. Old, Millicent Higgins (retired), Cashell Jaquish, Martha Lundberg, Mariana Gerschenson. In addition, we acknowledge Brigitt Heier and Marilyn Knowles for assistance in the preparation of this manuscript. We also thank the University of Minnesota Supercomputing Institute for Digital Simulation and Advanced Computation for use of the IBM SP supercomputer. ",

year = "2005",

month = mar,

doi = "10.1016/j.atherosclerosis.2004.09.009",

language = "English",

volume = "179",

pages = "119--125",

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TY - JOUR

T1 - Evidence for a gene influencing fasting LDL cholesterol and triglyceride levels on chromosome 21q

AU - North, Kari E.

AU - Miller, Michael B.

AU - Coon, Hilary

AU - Martin, Lisa J.

AU - Peacock, James M.

AU - Arnett, Donna

AU - Zhang, Binbin

AU - Province, Michael

AU - Oberman, Albert

AU - Blangero, John

AU - Almasy, Laura

AU - Ellison, R. Curtis

AU - Heiss, Gerardo

N1 - Funding Information: We wish to first acknowledge the participants of the HyperGEN study. This hypertension network is funded by cooperative agreements (U10) with NHLBI: HL54471, HL54472, HL54473, HL54495, HL54496, HL54497, HL54509, HL54515. We also acknowledge the HyperGEN Participating Institutions and Principal Staff: Network Center/University of Utah Field Center: Steven C. Hunt, Roger R. Williams (deceased), Hilary Coon, Paul N. Hopkins, Janet Hood, Lily Wu, Jan Skuppin; University of Alabama at Birmingham Field Center: Albert Oberman, Cora E. Lewis, Michael T. Weaver, Phillip Johnson, Susan Walker, Christie Oden; Boston University/Framingham Field Center: R. Curtis Ellison, Richard H. Myers, Yuqing Zhang, Luc Djoussé, Jemma B. Wilk, Greta Lee Splansky; University of Minnesota Field Center: Donna Arnett, Aaron R. Folsom, Mike Miller, Jim Pankow, Gregory Feitl, Barb Lux; University of North Carolina Field Center: Gerardo Heiss, Barry I. Freedman, Kari North, Kathryn Rose, Amy Haire; Data Coordinating Center,Washington University: D.C. Rao, Michael A. Province, Ingrid B. Borecki, Avril Adelman, Derek Morgan, Karen Schwander, David Lehner, Aldi Kraja, Stephen Mandel; Central Biochemistry Lab, University of Minnesota: John H. Eckfeldt, Ronald C. McGlennen, Michael Y. Tsai, Catherine Leiendecker-Foster, Greg Rynders, Jean Bucksa; Molecular Genetics Laboratory, University of Utah: Mark Leppert, Steven C. Hunt, Jean-Marc Lalouel, Robert Weiss; National Heart, Lung, & Blood Institute: Susan E. Old, Millicent Higgins (retired), Cashell Jaquish, Martha Lundberg, Mariana Gerschenson. In addition, we acknowledge Brigitt Heier and Marilyn Knowles for assistance in the preparation of this manuscript. We also thank the University of Minnesota Supercomputing Institute for Digital Simulation and Advanced Computation for use of the IBM SP supercomputer.

PY - 2005/3

Y1 - 2005/3

N2 - High levels of low-density lipoprotein (LDL) cholesterol, low levels of high-density lipoprotein (HDL) cholesterol, and high levels of triglycerides (TG) are strong predictors of cardiovascular disease risk. Motivated by previous evidence for pleiotropy between cholesterol and TG levels, we conducted bivariate linkage analysis of LDL cholesterol and TG concentration among participants of the Hypertension Genetic Epidemiolgy Network (HyperGEN), one of four networks in the NHLBI sponsored Family Blood Pressure Program Project. All available hypertensive siblings and their first-degree relatives were recruited. Both phenotypes were similarly adjusted for ethnicity, study center, sex, age, age-by-sex interactions, smoking, alcohol consumption, hormone use, diabetes medication use, and waist circumference. Variance component linkage analysis was performed as implemented in SOLAR, using ethnicity-specific marker allele frequencies derived from founders and multipoint IBDs calculated in MERLIN. A maximum genome-wide empirical LOD score of 3.9 was detected on chromosome 21 at 54 cM, between markers D21S2055 and D21S1446. This signal overlaps with suggestive and/or significant linkages for total cholesterol, LDL cholesterol, and apolipoprotein B in three other studies and is suggestive of one or more genes on chromosome 21q jointly regulating LDL cholesterol and TG concentration.

AB - High levels of low-density lipoprotein (LDL) cholesterol, low levels of high-density lipoprotein (HDL) cholesterol, and high levels of triglycerides (TG) are strong predictors of cardiovascular disease risk. Motivated by previous evidence for pleiotropy between cholesterol and TG levels, we conducted bivariate linkage analysis of LDL cholesterol and TG concentration among participants of the Hypertension Genetic Epidemiolgy Network (HyperGEN), one of four networks in the NHLBI sponsored Family Blood Pressure Program Project. All available hypertensive siblings and their first-degree relatives were recruited. Both phenotypes were similarly adjusted for ethnicity, study center, sex, age, age-by-sex interactions, smoking, alcohol consumption, hormone use, diabetes medication use, and waist circumference. Variance component linkage analysis was performed as implemented in SOLAR, using ethnicity-specific marker allele frequencies derived from founders and multipoint IBDs calculated in MERLIN. A maximum genome-wide empirical LOD score of 3.9 was detected on chromosome 21 at 54 cM, between markers D21S2055 and D21S1446. This signal overlaps with suggestive and/or significant linkages for total cholesterol, LDL cholesterol, and apolipoprotein B in three other studies and is suggestive of one or more genes on chromosome 21q jointly regulating LDL cholesterol and TG concentration.

KW - Cholesterol

KW - Linkage (genetics)

KW - Lipids

KW - Triglycerides

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Evidence for a gene influencing fasting LDL cholesterol and triglyceride levels on chromosome 21q

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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