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  • Title: Heritability and linkage analysis for carotid intima-media thickness: the family study of stroke risk and carotid atherosclerosis.
    Author: Sacco RL, Blanton SH, Slifer S, Beecham A, Glover K, Gardener H, Wang L, Sabala E, Juo SH, Rundek T.
    Journal: Stroke; 2009 Jul; 40(7):2307-12. PubMed ID: 19498180.
    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.
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