Heritability and linkage analysis for carotid intima-media thickness: The family study of stroke risk and carotid atherosclerosis

Ralph L Sacco, Susan H Blanton, Susan Slifer, Ashley Beecham, Khaleelah Glover, Hannah Gardener, Liyong Wang, Edison Sabala, Suh Hang Hank Juo, Tatjana Rundek

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Background and Purpose-The aim of this study was to identify quantitative trait loci (QTL) for carotid intima-media thickness (CIMT) a risk factor for stroke and cardiovascular disease. Methods-Probands were selected from Caribbean Hispanic subjects of the population-based Northern Manhattan Study. CIMT was measured by high-resolution B-mode ultrasound and expressed as the mean (IMTx) and mean of the maximum (IMTm). Variance components methodology was used to detect linkage using SOLAR and calculate locus-specific heritability. Ordered-subset Analysis was done based on history of hypertension and total cholesterol levels. Results-Among 100 Dominican families, 1390 subjects had CIMT measured (848 females; mean age 46.2 years). CIMT had a heritability of 0.65 after adjusting for age, age 2, sex, cigarette pack-years, waist hip ratio, and BMI. Adjusted maximum multipoint LOD scores >2 were found on chromosomes 14q (D14S606) and 7p (D7S817). Linkage to chromosome 14q was significantly increased in a subset of families with the greatest history of hypertension (MLOD=4.12). The QTL on Ch14q accounted for 0.21 of the heritability of IMTm, and on Ch7p 0.27 of the heritability of BIFm. Conclusions-Several QTLs for CIMT were found on chromosomes 7p and 14q. The QTL on 14q replicates a suggestive linkage peak delimited in the Framingham Heart Study. These QTLs accounted for a substantial amount of trait heritability and warrant further fine mapping.

Original languageEnglish
Pages (from-to)2307-2312
Number of pages6
JournalStroke
Volume40
Issue number7
DOIs
StatePublished - Jul 1 2009

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Carotid Intima-Media Thickness
Carotid Artery Diseases
Stroke
Quantitative Trait Loci
Chromosomes
Hypertension
Waist-Hip Ratio
Hispanic Americans
Tobacco Products
Cardiovascular Diseases
History
Cholesterol
Population

Keywords

  • Carotid disease
  • Genetics
  • Linkage
  • Quantitative traits
  • Risk factors

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Advanced and Specialized Nursing

Cite this

Heritability and linkage analysis for carotid intima-media thickness : The family study of stroke risk and carotid atherosclerosis. / Sacco, Ralph L; Blanton, Susan H; Slifer, Susan; Beecham, Ashley; Glover, Khaleelah; Gardener, Hannah; Wang, Liyong; Sabala, Edison; Hank Juo, Suh Hang; Rundek, Tatjana.

In: Stroke, Vol. 40, No. 7, 01.07.2009, p. 2307-2312.

Research output: Contribution to journalArticle

Sacco, Ralph L ; Blanton, Susan H ; Slifer, Susan ; Beecham, Ashley ; Glover, Khaleelah ; Gardener, Hannah ; Wang, Liyong ; Sabala, Edison ; Hank Juo, Suh Hang ; Rundek, Tatjana. / Heritability and linkage analysis for carotid intima-media thickness : The family study of stroke risk and carotid atherosclerosis. In: Stroke. 2009 ; Vol. 40, No. 7. pp. 2307-2312.
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AU - Blanton, Susan H

AU - Slifer, Susan

AU - Beecham, Ashley

AU - Glover, Khaleelah

AU - Gardener, Hannah

AU - Wang, Liyong

AU - Sabala, Edison

AU - Hank Juo, Suh Hang

AU - Rundek, Tatjana

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AB - Background and Purpose-The aim of this study was to identify quantitative trait loci (QTL) for carotid intima-media thickness (CIMT) a risk factor for stroke and cardiovascular disease. Methods-Probands were selected from Caribbean Hispanic subjects of the population-based Northern Manhattan Study. CIMT was measured by high-resolution B-mode ultrasound and expressed as the mean (IMTx) and mean of the maximum (IMTm). Variance components methodology was used to detect linkage using SOLAR and calculate locus-specific heritability. Ordered-subset Analysis was done based on history of hypertension and total cholesterol levels. Results-Among 100 Dominican families, 1390 subjects had CIMT measured (848 females; mean age 46.2 years). CIMT had a heritability of 0.65 after adjusting for age, age 2, sex, cigarette pack-years, waist hip ratio, and BMI. Adjusted maximum multipoint LOD scores >2 were found on chromosomes 14q (D14S606) and 7p (D7S817). Linkage to chromosome 14q was significantly increased in a subset of families with the greatest history of hypertension (MLOD=4.12). The QTL on Ch14q accounted for 0.21 of the heritability of IMTm, and on Ch7p 0.27 of the heritability of BIFm. Conclusions-Several QTLs for CIMT were found on chromosomes 7p and 14q. The QTL on 14q replicates a suggestive linkage peak delimited in the Framingham Heart Study. These QTLs accounted for a substantial amount of trait heritability and warrant further fine mapping.

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KW - Risk factors

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