Linkage analysis of plasma ApoE in three ethnic groups: Multiple genes with context-dependent effects

Kathy L E Klos, S. L R Kardia, J. E. Hixson, Stephen T Turner, C. Hanis, E. Boerwinkle, C. F. Sing

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

We performed variance component-based linkage analysis in four samples (two of non-Hispanic European-Americans from Rochester, MN; African-Americans from Jackson, MS; and Mexican-Americans from Starr County, TX) to identify chromosomal regions containing genes influencing plasma apolipoprotein E (apoE) levels. The APOE gene region on chromosome (chr) 19 was identified with a LOD ≥ 2.00 in both samples from Rochester and the sample from Jackson. Adjustment of apoE levels for differences among means of genotypes defined by the APOE ε 2/3/4 alleles reduced evidence of linkage, indicating that the APOE gene was responsible for the majority of the linkage signal. In stratified linkage analyses, there was a LOD of 1.70 in the Starr County sibships with average total cholesterol (TC) above the median level for all sibships in that population. Adjustment for APOE genotype did not remove this LOD score, suggesting a second gene in this region may influence apoE variation. Evidence of linkage (LOD = 3.32) on chr 17 was observed in the Starr County sibships with average TC below the median. Inter-individual variation in plasma apoE level may be influenced by variations in the structural gene, and at least one other gene whose effects differ among populations and are dependent on the influence of unmeasured genetic and environmental factors indexed by correlated measures of lipid metabolism.

Original languageEnglish (US)
Pages (from-to)157-167
Number of pages11
JournalAnnals of Human Genetics
Volume69
Issue number2
DOIs
StatePublished - Mar 2005

Fingerprint

Apolipoproteins E
Ethnic Groups
Genes
Cholesterol
Genotype
Chromosomes, Human, Pair 19
Chromosomes, Human, Pair 17
Lipid Metabolism
African Americans
Population
Alleles

Keywords

  • APOE
  • Apolipoprotein E
  • Genome scan
  • Sample stratification

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Linkage analysis of plasma ApoE in three ethnic groups : Multiple genes with context-dependent effects. / Klos, Kathy L E; Kardia, S. L R; Hixson, J. E.; Turner, Stephen T; Hanis, C.; Boerwinkle, E.; Sing, C. F.

In: Annals of Human Genetics, Vol. 69, No. 2, 03.2005, p. 157-167.

Research output: Contribution to journalArticle

Klos, Kathy L E ; Kardia, S. L R ; Hixson, J. E. ; Turner, Stephen T ; Hanis, C. ; Boerwinkle, E. ; Sing, C. F. / Linkage analysis of plasma ApoE in three ethnic groups : Multiple genes with context-dependent effects. In: Annals of Human Genetics. 2005 ; Vol. 69, No. 2. pp. 157-167.
@article{43cf6279033e4b6299f8a651abb9b4c1,
title = "Linkage analysis of plasma ApoE in three ethnic groups: Multiple genes with context-dependent effects",
abstract = "We performed variance component-based linkage analysis in four samples (two of non-Hispanic European-Americans from Rochester, MN; African-Americans from Jackson, MS; and Mexican-Americans from Starr County, TX) to identify chromosomal regions containing genes influencing plasma apolipoprotein E (apoE) levels. The APOE gene region on chromosome (chr) 19 was identified with a LOD ≥ 2.00 in both samples from Rochester and the sample from Jackson. Adjustment of apoE levels for differences among means of genotypes defined by the APOE ε 2/3/4 alleles reduced evidence of linkage, indicating that the APOE gene was responsible for the majority of the linkage signal. In stratified linkage analyses, there was a LOD of 1.70 in the Starr County sibships with average total cholesterol (TC) above the median level for all sibships in that population. Adjustment for APOE genotype did not remove this LOD score, suggesting a second gene in this region may influence apoE variation. Evidence of linkage (LOD = 3.32) on chr 17 was observed in the Starr County sibships with average TC below the median. Inter-individual variation in plasma apoE level may be influenced by variations in the structural gene, and at least one other gene whose effects differ among populations and are dependent on the influence of unmeasured genetic and environmental factors indexed by correlated measures of lipid metabolism.",
keywords = "APOE, Apolipoprotein E, Genome scan, Sample stratification",
author = "Klos, {Kathy L E} and Kardia, {S. L R} and Hixson, {J. E.} and Turner, {Stephen T} and C. Hanis and E. Boerwinkle and Sing, {C. F.}",
year = "2005",
month = "3",
doi = "10.1046/j.1529-8817.2004.00148.x",
language = "English (US)",
volume = "69",
pages = "157--167",
journal = "Annals of Human Genetics",
issn = "0003-4800",
publisher = "Wiley-Blackwell",
number = "2",

}

TY - JOUR

T1 - Linkage analysis of plasma ApoE in three ethnic groups

T2 - Multiple genes with context-dependent effects

AU - Klos, Kathy L E

AU - Kardia, S. L R

AU - Hixson, J. E.

AU - Turner, Stephen T

AU - Hanis, C.

AU - Boerwinkle, E.

AU - Sing, C. F.

PY - 2005/3

Y1 - 2005/3

N2 - We performed variance component-based linkage analysis in four samples (two of non-Hispanic European-Americans from Rochester, MN; African-Americans from Jackson, MS; and Mexican-Americans from Starr County, TX) to identify chromosomal regions containing genes influencing plasma apolipoprotein E (apoE) levels. The APOE gene region on chromosome (chr) 19 was identified with a LOD ≥ 2.00 in both samples from Rochester and the sample from Jackson. Adjustment of apoE levels for differences among means of genotypes defined by the APOE ε 2/3/4 alleles reduced evidence of linkage, indicating that the APOE gene was responsible for the majority of the linkage signal. In stratified linkage analyses, there was a LOD of 1.70 in the Starr County sibships with average total cholesterol (TC) above the median level for all sibships in that population. Adjustment for APOE genotype did not remove this LOD score, suggesting a second gene in this region may influence apoE variation. Evidence of linkage (LOD = 3.32) on chr 17 was observed in the Starr County sibships with average TC below the median. Inter-individual variation in plasma apoE level may be influenced by variations in the structural gene, and at least one other gene whose effects differ among populations and are dependent on the influence of unmeasured genetic and environmental factors indexed by correlated measures of lipid metabolism.

AB - We performed variance component-based linkage analysis in four samples (two of non-Hispanic European-Americans from Rochester, MN; African-Americans from Jackson, MS; and Mexican-Americans from Starr County, TX) to identify chromosomal regions containing genes influencing plasma apolipoprotein E (apoE) levels. The APOE gene region on chromosome (chr) 19 was identified with a LOD ≥ 2.00 in both samples from Rochester and the sample from Jackson. Adjustment of apoE levels for differences among means of genotypes defined by the APOE ε 2/3/4 alleles reduced evidence of linkage, indicating that the APOE gene was responsible for the majority of the linkage signal. In stratified linkage analyses, there was a LOD of 1.70 in the Starr County sibships with average total cholesterol (TC) above the median level for all sibships in that population. Adjustment for APOE genotype did not remove this LOD score, suggesting a second gene in this region may influence apoE variation. Evidence of linkage (LOD = 3.32) on chr 17 was observed in the Starr County sibships with average TC below the median. Inter-individual variation in plasma apoE level may be influenced by variations in the structural gene, and at least one other gene whose effects differ among populations and are dependent on the influence of unmeasured genetic and environmental factors indexed by correlated measures of lipid metabolism.

KW - APOE

KW - Apolipoprotein E

KW - Genome scan

KW - Sample stratification

UR - http://www.scopus.com/inward/record.url?scp=14944383241&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=14944383241&partnerID=8YFLogxK

U2 - 10.1046/j.1529-8817.2004.00148.x

DO - 10.1046/j.1529-8817.2004.00148.x

M3 - Article

C2 - 15720297

AN - SCOPUS:14944383241

VL - 69

SP - 157

EP - 167

JO - Annals of Human Genetics

JF - Annals of Human Genetics

SN - 0003-4800

IS - 2

ER -