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

40 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

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

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