Published Online
on March 6, 2008

A more recent version of this article appeared on April 1, 2008

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Submitted on April 4, 2007
Revised on July 2, 2007
Accepted on July 20, 2007

A Whole-Genome Scan for Stroke or Myocardial Infarction in Family Blood Pressure Program Families

Richard Sherva PhD; Michael B. Miller PhD; James S. Pankow PhD; Steven C. Hunt PhD; Eric Boerwinkle PhD; Thomas H. Mosley PhD; Alan B. Weder MD; J. David Curb MD; Amy Luke MD; Alanna C. Morrison PhD; Myriam Fornage PhD; and Donna K. Arnett PhD^*

From the Division of Epidemiology and Community Health (R.S., M.B.M., J.S.P.), University of Minnesota, Minneapolis, Minn; the Cardiovascular Genetics Division (S.C.H.), University of Utah School of Medicine, Salt Lake City, Utah; the Human Genetics Center (E.B.) and the Institute of Molecular Medicine (E.B.), University of Texas–Houston Health Science Center, Houston, Texas; the Department of Medicine (T.H.M.), University of Mississippi Medical Center, Jackson, Miss; the Division of Hypertension (A.B.W.), University of Michigan School of Medicine, Ann Arbor, Mich; the Pacific Health Research Institute (J.D.C.), Honolulu, Hawaii; the Department of Preventative Medicine and Epidemiology (A.L.), Loyola University Strich School of Medicine, Maywood, Ill; the Human Genetics Center (A.C.M.), University of Texas at Houston, Houston, Texas; the Institute of Molecular Medicine for the Prevention of Human Diseases (M.F.), University of Texas Health Science Center, Houston, Texas; and the Department of Epidemiology (D.K.A.), University of Alabama Birmingham, Ala.

^* To whom correspondence should be addressed. E-mail: arnett{at}uab.edu.

Background and Purpose—Atherothrombotic diseases, including stroke and myocardial infarction, share a common pathogenesis. Chromosomal regions have been linked to atherothrombotic diseases in family studies, and association studies have identified candidate gene polymorphisms that affect the risk of stroke and/or myocardial infarction. Using data from the Family Blood Pressure Program, we tested for chromosomal regions linked to the composite phenotype of stroke or myocardial infarction in a large set of hypertensive families.

Methods—Nonparametric linkage analysis was implemented in MERLIN, which tests for excess allele-sharing among affected siblings. Empirical distributions based on gene dropping simulations were constructed for each test statistic, and the -log₁₀ of the associated probability values were compared.

Results—Analyses were based on 9607 individuals in 226 black, 395 Hispanic, and 207 white families; 106 families had multiple affected individuals. Several regions showed linkage to stroke or myocardial infarction, most significantly in Hispanics on chromosomes 2p21 (-log₁₀ P=3.0) and 7q21.1 (-log₁₀ P=2.8), 9q32 in blacks and Hispanics (-log₁₀ P=3.0), 11p13 in blacks (-log₁₀ P=2.1), and 12q24.33 in whites (-log₁₀ P=3.0).

Conclusions—There is statistically significant evidence for loci affecting stroke or myocardial infarction on chromosomes 2, 9, and 12.

Key words: cerebrovascular accident • epidemiology • linkage (genetics) • LOD score • myocardial infarction

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