Meta-analysis of genome-wide linkage studies for quantitative lipid traits in African Americans

Alka Malhotra, Hilary Coon, Mary F. Feitosa, Wei Dong Li, Kari E. North, R. Arlen Price, Claude Bouchard, Steven Hunt, Johanna K. Wolford, Eric Boerwinkle, John Buse, Ralph DeFronzo, David Ehrmann, Steven C. Elbein, Wilfred Fujimoto, Steven E. Kahn, Craig L. Hanis, Richard A. Mulivor, Jeanne C. Beck, Jill Norris & 4 others M. Alan Permutt, Philip Behn, Leslie Raffel, David C. Robbins

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Genetic influences on lipid traits have been suggested by numerous studies. In addition to heritability studies, over 50 genome scans have been performed to identify regions of linkage for quantitative lipid levels. Five of these scans have been performed in African Americans (four univariate and one bivariate linkage analysis), but with results that have been largely inconclusive. Linkage analyses are often limited by both sample size and heterogeneity, which may lead to nominal LOD scores or lack of evidence for linkage; the use of meta-analysis to combine linkage results from populations with similar ethnic backgrounds may help overcome some of these limitations. Thus, we performed a meta-analysis using data from four genome scans conducted in African American families to identify chromosomal regions showing evidence of linkage for total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL) and high density lipoprotein cholesterol (HDL). Significant evidence (i.e. P < 0.00042) for linkage was found for LDL on chromosome 1q32.1-q41 (Pweighted = 0.00014 and Punweighted = 0.00007) and 1q41-q44 (Pweighted = 0.00017 and Punweighted = 0.00014). We found suggestive evidence (i.e. P<0.00847) for TG on 16p12.1-q11.2 and for HDL on 4p15.1-p11. We also assessed heterogeneity between studies and found significant evidence for low heterogeneity for both regions on chromosome 1q (P = 0.0300 and P = 0.0279, respectively) for LDL and chromosome 16 (P = 0.0429) for TG. Statistically significant evidence for linkage and low heterogeneity on chromosome 1q therefore suggest that this region may harbor a gene underlying the inheritance of LDL in African Americans.

Original languageEnglish
Pages (from-to)3955-3962
Number of pages8
JournalHuman Molecular Genetics
Volume14
Issue number24
DOIs
Publication statusPublished - 15 Dec 2005
Externally publishedYes

Fingerprint

African Americans
LDL Cholesterol
Meta-Analysis
Genome
Lipids
Triglycerides
Chromosomes
HDL Cholesterol
Chromosomes, Human, Pair 16
Sample Size
Cholesterol
Population
Genes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Malhotra, A., Coon, H., Feitosa, M. F., Li, W. D., North, K. E., Price, R. A., ... Robbins, D. C. (2005). Meta-analysis of genome-wide linkage studies for quantitative lipid traits in African Americans. Human Molecular Genetics, 14(24), 3955-3962. https://doi.org/10.1093/hmg/ddi419

Meta-analysis of genome-wide linkage studies for quantitative lipid traits in African Americans. / Malhotra, Alka; Coon, Hilary; Feitosa, Mary F.; Li, Wei Dong; North, Kari E.; Price, R. Arlen; Bouchard, Claude; Hunt, Steven; Wolford, Johanna K.; Boerwinkle, Eric; Buse, John; DeFronzo, Ralph; Ehrmann, David; Elbein, Steven C.; Fujimoto, Wilfred; Kahn, Steven E.; Hanis, Craig L.; Mulivor, Richard A.; Beck, Jeanne C.; Norris, Jill; Permutt, M. Alan; Behn, Philip; Raffel, Leslie; Robbins, David C.

In: Human Molecular Genetics, Vol. 14, No. 24, 15.12.2005, p. 3955-3962.

Research output: Contribution to journalArticle

Malhotra, A, Coon, H, Feitosa, MF, Li, WD, North, KE, Price, RA, Bouchard, C, Hunt, S, Wolford, JK, Boerwinkle, E, Buse, J, DeFronzo, R, Ehrmann, D, Elbein, SC, Fujimoto, W, Kahn, SE, Hanis, CL, Mulivor, RA, Beck, JC, Norris, J, Permutt, MA, Behn, P, Raffel, L & Robbins, DC 2005, 'Meta-analysis of genome-wide linkage studies for quantitative lipid traits in African Americans', Human Molecular Genetics, vol. 14, no. 24, pp. 3955-3962. https://doi.org/10.1093/hmg/ddi419
Malhotra, Alka ; Coon, Hilary ; Feitosa, Mary F. ; Li, Wei Dong ; North, Kari E. ; Price, R. Arlen ; Bouchard, Claude ; Hunt, Steven ; Wolford, Johanna K. ; Boerwinkle, Eric ; Buse, John ; DeFronzo, Ralph ; Ehrmann, David ; Elbein, Steven C. ; Fujimoto, Wilfred ; Kahn, Steven E. ; Hanis, Craig L. ; Mulivor, Richard A. ; Beck, Jeanne C. ; Norris, Jill ; Permutt, M. Alan ; Behn, Philip ; Raffel, Leslie ; Robbins, David C. / Meta-analysis of genome-wide linkage studies for quantitative lipid traits in African Americans. In: Human Molecular Genetics. 2005 ; Vol. 14, No. 24. pp. 3955-3962.
@article{07d7811801a44708939eac8104998518,
title = "Meta-analysis of genome-wide linkage studies for quantitative lipid traits in African Americans",
abstract = "Genetic influences on lipid traits have been suggested by numerous studies. In addition to heritability studies, over 50 genome scans have been performed to identify regions of linkage for quantitative lipid levels. Five of these scans have been performed in African Americans (four univariate and one bivariate linkage analysis), but with results that have been largely inconclusive. Linkage analyses are often limited by both sample size and heterogeneity, which may lead to nominal LOD scores or lack of evidence for linkage; the use of meta-analysis to combine linkage results from populations with similar ethnic backgrounds may help overcome some of these limitations. Thus, we performed a meta-analysis using data from four genome scans conducted in African American families to identify chromosomal regions showing evidence of linkage for total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL) and high density lipoprotein cholesterol (HDL). Significant evidence (i.e. P < 0.00042) for linkage was found for LDL on chromosome 1q32.1-q41 (Pweighted = 0.00014 and Punweighted = 0.00007) and 1q41-q44 (Pweighted = 0.00017 and Punweighted = 0.00014). We found suggestive evidence (i.e. P<0.00847) for TG on 16p12.1-q11.2 and for HDL on 4p15.1-p11. We also assessed heterogeneity between studies and found significant evidence for low heterogeneity for both regions on chromosome 1q (P = 0.0300 and P = 0.0279, respectively) for LDL and chromosome 16 (P = 0.0429) for TG. Statistically significant evidence for linkage and low heterogeneity on chromosome 1q therefore suggest that this region may harbor a gene underlying the inheritance of LDL in African Americans.",
author = "Alka Malhotra and Hilary Coon and Feitosa, {Mary F.} and Li, {Wei Dong} and North, {Kari E.} and Price, {R. Arlen} and Claude Bouchard and Steven Hunt and Wolford, {Johanna K.} and Eric Boerwinkle and John Buse and Ralph DeFronzo and David Ehrmann and Elbein, {Steven C.} and Wilfred Fujimoto and Kahn, {Steven E.} and Hanis, {Craig L.} and Mulivor, {Richard A.} and Beck, {Jeanne C.} and Jill Norris and Permutt, {M. Alan} and Philip Behn and Leslie Raffel and Robbins, {David C.}",
year = "2005",
month = "12",
day = "15",
doi = "10.1093/hmg/ddi419",
language = "English",
volume = "14",
pages = "3955--3962",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "24",

}

TY - JOUR

T1 - Meta-analysis of genome-wide linkage studies for quantitative lipid traits in African Americans

AU - Malhotra, Alka

AU - Coon, Hilary

AU - Feitosa, Mary F.

AU - Li, Wei Dong

AU - North, Kari E.

AU - Price, R. Arlen

AU - Bouchard, Claude

AU - Hunt, Steven

AU - Wolford, Johanna K.

AU - Boerwinkle, Eric

AU - Buse, John

AU - DeFronzo, Ralph

AU - Ehrmann, David

AU - Elbein, Steven C.

AU - Fujimoto, Wilfred

AU - Kahn, Steven E.

AU - Hanis, Craig L.

AU - Mulivor, Richard A.

AU - Beck, Jeanne C.

AU - Norris, Jill

AU - Permutt, M. Alan

AU - Behn, Philip

AU - Raffel, Leslie

AU - Robbins, David C.

PY - 2005/12/15

Y1 - 2005/12/15

N2 - Genetic influences on lipid traits have been suggested by numerous studies. In addition to heritability studies, over 50 genome scans have been performed to identify regions of linkage for quantitative lipid levels. Five of these scans have been performed in African Americans (four univariate and one bivariate linkage analysis), but with results that have been largely inconclusive. Linkage analyses are often limited by both sample size and heterogeneity, which may lead to nominal LOD scores or lack of evidence for linkage; the use of meta-analysis to combine linkage results from populations with similar ethnic backgrounds may help overcome some of these limitations. Thus, we performed a meta-analysis using data from four genome scans conducted in African American families to identify chromosomal regions showing evidence of linkage for total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL) and high density lipoprotein cholesterol (HDL). Significant evidence (i.e. P < 0.00042) for linkage was found for LDL on chromosome 1q32.1-q41 (Pweighted = 0.00014 and Punweighted = 0.00007) and 1q41-q44 (Pweighted = 0.00017 and Punweighted = 0.00014). We found suggestive evidence (i.e. P<0.00847) for TG on 16p12.1-q11.2 and for HDL on 4p15.1-p11. We also assessed heterogeneity between studies and found significant evidence for low heterogeneity for both regions on chromosome 1q (P = 0.0300 and P = 0.0279, respectively) for LDL and chromosome 16 (P = 0.0429) for TG. Statistically significant evidence for linkage and low heterogeneity on chromosome 1q therefore suggest that this region may harbor a gene underlying the inheritance of LDL in African Americans.

AB - Genetic influences on lipid traits have been suggested by numerous studies. In addition to heritability studies, over 50 genome scans have been performed to identify regions of linkage for quantitative lipid levels. Five of these scans have been performed in African Americans (four univariate and one bivariate linkage analysis), but with results that have been largely inconclusive. Linkage analyses are often limited by both sample size and heterogeneity, which may lead to nominal LOD scores or lack of evidence for linkage; the use of meta-analysis to combine linkage results from populations with similar ethnic backgrounds may help overcome some of these limitations. Thus, we performed a meta-analysis using data from four genome scans conducted in African American families to identify chromosomal regions showing evidence of linkage for total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL) and high density lipoprotein cholesterol (HDL). Significant evidence (i.e. P < 0.00042) for linkage was found for LDL on chromosome 1q32.1-q41 (Pweighted = 0.00014 and Punweighted = 0.00007) and 1q41-q44 (Pweighted = 0.00017 and Punweighted = 0.00014). We found suggestive evidence (i.e. P<0.00847) for TG on 16p12.1-q11.2 and for HDL on 4p15.1-p11. We also assessed heterogeneity between studies and found significant evidence for low heterogeneity for both regions on chromosome 1q (P = 0.0300 and P = 0.0279, respectively) for LDL and chromosome 16 (P = 0.0429) for TG. Statistically significant evidence for linkage and low heterogeneity on chromosome 1q therefore suggest that this region may harbor a gene underlying the inheritance of LDL in African Americans.

UR - http://www.scopus.com/inward/record.url?scp=29644437151&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=29644437151&partnerID=8YFLogxK

U2 - 10.1093/hmg/ddi419

DO - 10.1093/hmg/ddi419

M3 - Article

VL - 14

SP - 3955

EP - 3962

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 24

ER -