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

Stroke. 2009 Jul;40(7):2307-12. doi: 10.1161/STROKEAHA.109.554121. Epub 2009 Jun 4.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Carotid Arteries / diagnostic imaging*
  • Carotid Artery Diseases / ethnology
  • Carotid Artery Diseases / genetics*
  • Chromosome Mapping
  • Chromosomes, Human, Pair 14 / genetics
  • Chromosomes, Human, Pair 7 / genetics
  • Female
  • Genetic Linkage / genetics*
  • Genetic Predisposition to Disease / genetics
  • Genotype
  • Hispanic or Latino / ethnology
  • Hispanic or Latino / genetics
  • Humans
  • Male
  • Middle Aged
  • Phenotype
  • Quantitative Trait Loci / genetics
  • Risk Factors
  • Stroke / ethnology
  • Stroke / genetics*
  • Tunica Intima / diagnostic imaging*
  • Tunica Media / diagnostic imaging*
  • Ultrasonography
  • West Indies