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

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.

journal_name

Stroke

journal_title

Stroke

authors

Sacco RL,Blanton SH,Slifer S,Beecham A,Glover K,Gardener H,Wang L,Sabala E,Juo SH,Rundek T

doi

10.1161/STROKEAHA.109.554121

subject

Has Abstract

pub_date

2009-07-01 00:00:00

pages

2307-12

issue

7

eissn

0039-2499

issn

1524-4628

pii

STROKEAHA.109.554121

journal_volume

40

pub_type

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