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(Stroke. 2009;40:2307.)
© 2009 American Heart Association, Inc.

Original Contributions

Heritability and Linkage Analysis for Carotid Intima-Media Thickness

The Family Study of Stroke Risk and Carotid Atherosclerosis

Ralph L. Sacco, MD, MS; Susan H. Blanton, PhD; Susan Slifer, MS; Ashley Beecham, MS; Khaleelah Glover, MS; Hannah Gardener, ScD; Liyong Wang, PhD; Edison Sabala, MPH; Suh-Hang Hank Juo, MD, PhD Tatjana Rundek, MD, PhD

From the Department of Neurology (R.L.S., H.G., E.S., T.R.) and Human Genetics (R.L.S., S.H.B., S.S., A.B., K.G., L.W.), Miller School of Medicine, University of Miami, Fla; and the Department and Graduate Program of Medical Genetics (S.-H.H.J.), Kaohsiung Medical University, Taiwan.

Correspondence to Ralph L. Sacco, MD, University of Miami, 1120 NW 14th Street, Miami, FL 33136. E-mail rsacco{at}med.miami.edu

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, age², 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.

Key Words: carotid disease • genetics • linkage • quantitative traits • risk factors