Evidence of QTL on 15q21 for high-density lipoprotein cholesterol: The National Heart, Lung, and Blood Institute Family Heart Study (NHLBI FHS)

Mary F. Feitosa; Michael A. Province; Gerardo Heiss; Donna K. Arnett; Richard H. Myers; James S. Pankow; Paul N. Hopkins; Ingrid B. Borecki

doi:10.1016/j.atherosclerosis.2006.02.006

Evidence of QTL on 15q21 for high-density lipoprotein cholesterol: The National Heart, Lung, and Blood Institute Family Heart Study (NHLBI FHS)

Mary F. Feitosa, Michael A. Province, Gerardo Heiss, Donna K. Arnett, Richard H. Myers, James S. Pankow, Paul N. Hopkins, Ingrid B. Borecki

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

9 Scopus citations

Abstract

A genome-wide linkage scan was conducted to identify regions potentially having quantitative trait loci (QTLs) influencing high-density lipoprotein (HDL) cholesterol. We found suggestive evidence of a QTL (lod score (LOD) = 1.75, p = 0.00224, and q = 0.07649) influencing the variation of plasma levels of age- and sex-adjusted HDL-cholesterol on chromosome 15q21 at marker D15S659 in the NHLBI FHS data. Owing to the perturbations to lipid profiles associated with diabetes, the analysis was repeated excluding diabetic subjects from the sample. The lod score increased from 1.75 to 2.71 (p = 0.00021, q = 0.05392) at the same chromosome 15 location, despite the reduction in sample size. This finding indicates that the inclusion of diabetic subjects in the analysis may confound the presence of a QTL for HDL-cholesterol on 15q21. Because of the known effects of important covariates such as metabolic variables and lifestyle habits that may interact with a putative QTL, we also analyzed HDL-cholesterol with a progressive adjustment. When body mass index, smoking, and habitual alcohol intake were added to age- and sex-adjustment, we found strong evidence for linkage in the complete sample (LOD = 4.77, p = 0.0000013, and q = 0.00016) as well as in the non-diabetic sub-sample (LOD = 4.52, p = 0.0000025, and q = 0.00026) on chromosome 15q21 (between D15S659 and D15S195 markers). These results suggest that there are multiple pathways and factors involving genetic and environmental effects influencing HDL-cholesterol levels, and by taking some of these known factors into account, we obtained strong evidence of a QTL influencing HDL-cholesterol levels. While this putative QTL may also have an effect in diabetes, our data suggest a more pronounced role in non-diabetics. A prominent candidate gene residing within the linkage region on 15q21 is hepatic lipase (HL), which has a major role in lipoprotein metabolism.

Original language	English
Pages (from-to)	232-237
Number of pages	6
Journal	Atherosclerosis
Volume	190
Issue number	1
DOIs	https://doi.org/10.1016/j.atherosclerosis.2006.02.006
State	Published - Jan 2007

Bibliographical note

Funding Information:
Support was provided by the National Heart, Lung, and Blood Institute cooperative agreement grants U01 HL 67893, U01 HL67894, U01 HL67895, U01 HL67896, U01 HL67897, U01 HL67898, U01 HL67899, U01 HL67900, U01 HL67901, and U01 HL67902. Support was also partially provided by the National Heart, Lung, and Blood Institute cooperative agreement grants U01 HL56563, U01 HL56564, U01 HL56565, U01 HL56566, U01 HL56567, U01 HL56568, and U01 HL56569. This report is presented on behalf of the investigators of the NHLBI Family Heart Study. The investigators thank the study participants and staff for their valuable contributions.

Funding

Support was provided by the National Heart, Lung, and Blood Institute cooperative agreement grants U01 HL 67893, U01 HL67894, U01 HL67895, U01 HL67896, U01 HL67897, U01 HL67898, U01 HL67899, U01 HL67900, U01 HL67901, and U01 HL67902. Support was also partially provided by the National Heart, Lung, and Blood Institute cooperative agreement grants U01 HL56563, U01 HL56564, U01 HL56565, U01 HL56566, U01 HL56567, U01 HL56568, and U01 HL56569. This report is presented on behalf of the investigators of the NHLBI Family Heart Study. The investigators thank the study participants and staff for their valuable contributions.

Funders	Funder number
National Heart, Lung, and Blood Institute (NHLBI)	U01 HL56568, U01 HL56569, U01 HL 67893, U01 HL56563, U01 HL56564, U01 HL56565, U01 HL56567, U01 HL67897, U01 HL67896, U01 HL67895, U01 HL67894, U01HL056566, U01 HL67902, U01 HL67901, U01 HL67900, U01 HL67899, U01 HL67898

Keywords

BMI
Covariate
Diabetes
Genetic epidemiology
HDL
Quantitative trait loci
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.2006.02.006

Cite this

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title = "Evidence of QTL on 15q21 for high-density lipoprotein cholesterol: The National Heart, Lung, and Blood Institute Family Heart Study (NHLBI FHS)",

abstract = "A genome-wide linkage scan was conducted to identify regions potentially having quantitative trait loci (QTLs) influencing high-density lipoprotein (HDL) cholesterol. We found suggestive evidence of a QTL (lod score (LOD) = 1.75, p = 0.00224, and q = 0.07649) influencing the variation of plasma levels of age- and sex-adjusted HDL-cholesterol on chromosome 15q21 at marker D15S659 in the NHLBI FHS data. Owing to the perturbations to lipid profiles associated with diabetes, the analysis was repeated excluding diabetic subjects from the sample. The lod score increased from 1.75 to 2.71 (p = 0.00021, q = 0.05392) at the same chromosome 15 location, despite the reduction in sample size. This finding indicates that the inclusion of diabetic subjects in the analysis may confound the presence of a QTL for HDL-cholesterol on 15q21. Because of the known effects of important covariates such as metabolic variables and lifestyle habits that may interact with a putative QTL, we also analyzed HDL-cholesterol with a progressive adjustment. When body mass index, smoking, and habitual alcohol intake were added to age- and sex-adjustment, we found strong evidence for linkage in the complete sample (LOD = 4.77, p = 0.0000013, and q = 0.00016) as well as in the non-diabetic sub-sample (LOD = 4.52, p = 0.0000025, and q = 0.00026) on chromosome 15q21 (between D15S659 and D15S195 markers). These results suggest that there are multiple pathways and factors involving genetic and environmental effects influencing HDL-cholesterol levels, and by taking some of these known factors into account, we obtained strong evidence of a QTL influencing HDL-cholesterol levels. While this putative QTL may also have an effect in diabetes, our data suggest a more pronounced role in non-diabetics. A prominent candidate gene residing within the linkage region on 15q21 is hepatic lipase (HL), which has a major role in lipoprotein metabolism.",

keywords = "BMI, Covariate, Diabetes, Genetic epidemiology, HDL, Quantitative trait loci, Triglycerides",

author = "Feitosa, {Mary F.} and Province, {Michael A.} and Gerardo Heiss and Arnett, {Donna K.} and Myers, {Richard H.} and Pankow, {James S.} and Hopkins, {Paul N.} and Borecki, {Ingrid B.}",

note = "Funding Information: Support was provided by the National Heart, Lung, and Blood Institute cooperative agreement grants U01 HL 67893, U01 HL67894, U01 HL67895, U01 HL67896, U01 HL67897, U01 HL67898, U01 HL67899, U01 HL67900, U01 HL67901, and U01 HL67902. Support was also partially provided by the National Heart, Lung, and Blood Institute cooperative agreement grants U01 HL56563, U01 HL56564, U01 HL56565, U01 HL56566, U01 HL56567, U01 HL56568, and U01 HL56569. This report is presented on behalf of the investigators of the NHLBI Family Heart Study. The investigators thank the study participants and staff for their valuable contributions.",

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doi = "10.1016/j.atherosclerosis.2006.02.006",

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T1 - Evidence of QTL on 15q21 for high-density lipoprotein cholesterol

T2 - The National Heart, Lung, and Blood Institute Family Heart Study (NHLBI FHS)

AU - Feitosa, Mary F.

AU - Province, Michael A.

AU - Heiss, Gerardo

AU - Arnett, Donna K.

AU - Myers, Richard H.

AU - Pankow, James S.

AU - Hopkins, Paul N.

AU - Borecki, Ingrid B.

N1 - Funding Information: Support was provided by the National Heart, Lung, and Blood Institute cooperative agreement grants U01 HL 67893, U01 HL67894, U01 HL67895, U01 HL67896, U01 HL67897, U01 HL67898, U01 HL67899, U01 HL67900, U01 HL67901, and U01 HL67902. Support was also partially provided by the National Heart, Lung, and Blood Institute cooperative agreement grants U01 HL56563, U01 HL56564, U01 HL56565, U01 HL56566, U01 HL56567, U01 HL56568, and U01 HL56569. This report is presented on behalf of the investigators of the NHLBI Family Heart Study. The investigators thank the study participants and staff for their valuable contributions.

PY - 2007/1

Y1 - 2007/1

N2 - A genome-wide linkage scan was conducted to identify regions potentially having quantitative trait loci (QTLs) influencing high-density lipoprotein (HDL) cholesterol. We found suggestive evidence of a QTL (lod score (LOD) = 1.75, p = 0.00224, and q = 0.07649) influencing the variation of plasma levels of age- and sex-adjusted HDL-cholesterol on chromosome 15q21 at marker D15S659 in the NHLBI FHS data. Owing to the perturbations to lipid profiles associated with diabetes, the analysis was repeated excluding diabetic subjects from the sample. The lod score increased from 1.75 to 2.71 (p = 0.00021, q = 0.05392) at the same chromosome 15 location, despite the reduction in sample size. This finding indicates that the inclusion of diabetic subjects in the analysis may confound the presence of a QTL for HDL-cholesterol on 15q21. Because of the known effects of important covariates such as metabolic variables and lifestyle habits that may interact with a putative QTL, we also analyzed HDL-cholesterol with a progressive adjustment. When body mass index, smoking, and habitual alcohol intake were added to age- and sex-adjustment, we found strong evidence for linkage in the complete sample (LOD = 4.77, p = 0.0000013, and q = 0.00016) as well as in the non-diabetic sub-sample (LOD = 4.52, p = 0.0000025, and q = 0.00026) on chromosome 15q21 (between D15S659 and D15S195 markers). These results suggest that there are multiple pathways and factors involving genetic and environmental effects influencing HDL-cholesterol levels, and by taking some of these known factors into account, we obtained strong evidence of a QTL influencing HDL-cholesterol levels. While this putative QTL may also have an effect in diabetes, our data suggest a more pronounced role in non-diabetics. A prominent candidate gene residing within the linkage region on 15q21 is hepatic lipase (HL), which has a major role in lipoprotein metabolism.

AB - A genome-wide linkage scan was conducted to identify regions potentially having quantitative trait loci (QTLs) influencing high-density lipoprotein (HDL) cholesterol. We found suggestive evidence of a QTL (lod score (LOD) = 1.75, p = 0.00224, and q = 0.07649) influencing the variation of plasma levels of age- and sex-adjusted HDL-cholesterol on chromosome 15q21 at marker D15S659 in the NHLBI FHS data. Owing to the perturbations to lipid profiles associated with diabetes, the analysis was repeated excluding diabetic subjects from the sample. The lod score increased from 1.75 to 2.71 (p = 0.00021, q = 0.05392) at the same chromosome 15 location, despite the reduction in sample size. This finding indicates that the inclusion of diabetic subjects in the analysis may confound the presence of a QTL for HDL-cholesterol on 15q21. Because of the known effects of important covariates such as metabolic variables and lifestyle habits that may interact with a putative QTL, we also analyzed HDL-cholesterol with a progressive adjustment. When body mass index, smoking, and habitual alcohol intake were added to age- and sex-adjustment, we found strong evidence for linkage in the complete sample (LOD = 4.77, p = 0.0000013, and q = 0.00016) as well as in the non-diabetic sub-sample (LOD = 4.52, p = 0.0000025, and q = 0.00026) on chromosome 15q21 (between D15S659 and D15S195 markers). These results suggest that there are multiple pathways and factors involving genetic and environmental effects influencing HDL-cholesterol levels, and by taking some of these known factors into account, we obtained strong evidence of a QTL influencing HDL-cholesterol levels. While this putative QTL may also have an effect in diabetes, our data suggest a more pronounced role in non-diabetics. A prominent candidate gene residing within the linkage region on 15q21 is hepatic lipase (HL), which has a major role in lipoprotein metabolism.

KW - BMI

KW - Covariate

KW - Diabetes

KW - Genetic epidemiology

KW - HDL

KW - Quantitative trait loci

KW - Triglycerides

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VL - 190

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JO - Atherosclerosis

JF - Atherosclerosis

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Evidence of QTL on 15q21 for high-density lipoprotein cholesterol: The National Heart, Lung, and Blood Institute Family Heart Study (NHLBI FHS)

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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