Genome-wide scan for white matter hyperintensity: The framingham heart study

Anita L. DeStefano, Larry D. Atwood, Joseph M. Massaro, Nancy Heard-Costa, Alexa Beiser, Rhoda Au, Philip A. Wolf, Charles DeCarli

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Background and Purpose - White matter hyperintensity (WMH) volume is associated with aging and cerebrovascular disease and has been demonstrated to have a high heritability in the Framingham Heart Study as well as in other studies. We performed a genome-wide linkage analysis to identify chromosomal regions that may harbor genes influencing WMH in a family-based sample of the Framingham Heart Study. Methods - Brain magnetic resonance scans were performed, and WMH and total cranial volume (TCV) were quantified as previously described on 2259 cohort and offspring participants. The outcome used for linkage analysis was an age specific (within 10-year age groups) z-score for the natural logarithm of the ratio of WMH to TCV. This z-score was based on 2230 individuals after excluding 26 participants with neurological conditions other than stroke and 3 individuals whose ages were out of range. Variance component linkage analysis included 747 individuals (mean age=62.16±12.43 years) with both magnetic resonance measure and genotype information in 237 families. Mean percent WMH to TCV was 0.098±0.175 with a range of 0.00025% to 1.37% in the linkage analysis subjects. Results - A maximum multipoint logarithm of the odds (LOD) score=3.69, which indicates significant evidence of linkage, was observed at 4 cM on chromosome 4. A suggestive peak with LOD=1.78 was observed at 95 cM on chromosome 17. Conclusion - We have significant evidence that a gene influencing WMH volume is located on chromosome 4 of the human genome.

Original languageEnglish (US)
Pages (from-to)77-81
Number of pages5
JournalStroke
Volume37
Issue number1
DOIs
StatePublished - Jan 2006

Fingerprint

Genome
Chromosomes, Human, Pair 4
Magnetic Resonance Spectroscopy
Cerebrovascular Disorders
Chromosomes, Human, Pair 17
Human Genome
Genes
White Matter
Age Groups
Stroke
Genotype
Brain

Keywords

  • Aging
  • Cerebrovascular disorders
  • Linkage (genetics)

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Neuroscience(all)

Cite this

DeStefano, A. L., Atwood, L. D., Massaro, J. M., Heard-Costa, N., Beiser, A., Au, R., ... DeCarli, C. (2006). Genome-wide scan for white matter hyperintensity: The framingham heart study. Stroke, 37(1), 77-81. https://doi.org/10.1161/01.STR.0000196987.68770.b3

Genome-wide scan for white matter hyperintensity : The framingham heart study. / DeStefano, Anita L.; Atwood, Larry D.; Massaro, Joseph M.; Heard-Costa, Nancy; Beiser, Alexa; Au, Rhoda; Wolf, Philip A.; DeCarli, Charles.

In: Stroke, Vol. 37, No. 1, 01.2006, p. 77-81.

Research output: Contribution to journalArticle

DeStefano, AL, Atwood, LD, Massaro, JM, Heard-Costa, N, Beiser, A, Au, R, Wolf, PA & DeCarli, C 2006, 'Genome-wide scan for white matter hyperintensity: The framingham heart study', Stroke, vol. 37, no. 1, pp. 77-81. https://doi.org/10.1161/01.STR.0000196987.68770.b3
DeStefano AL, Atwood LD, Massaro JM, Heard-Costa N, Beiser A, Au R et al. Genome-wide scan for white matter hyperintensity: The framingham heart study. Stroke. 2006 Jan;37(1):77-81. https://doi.org/10.1161/01.STR.0000196987.68770.b3
DeStefano, Anita L. ; Atwood, Larry D. ; Massaro, Joseph M. ; Heard-Costa, Nancy ; Beiser, Alexa ; Au, Rhoda ; Wolf, Philip A. ; DeCarli, Charles. / Genome-wide scan for white matter hyperintensity : The framingham heart study. In: Stroke. 2006 ; Vol. 37, No. 1. pp. 77-81.
@article{8627b8c5d9184bf29e7cb36cafa4b9f4,
title = "Genome-wide scan for white matter hyperintensity: The framingham heart study",
abstract = "Background and Purpose - White matter hyperintensity (WMH) volume is associated with aging and cerebrovascular disease and has been demonstrated to have a high heritability in the Framingham Heart Study as well as in other studies. We performed a genome-wide linkage analysis to identify chromosomal regions that may harbor genes influencing WMH in a family-based sample of the Framingham Heart Study. Methods - Brain magnetic resonance scans were performed, and WMH and total cranial volume (TCV) were quantified as previously described on 2259 cohort and offspring participants. The outcome used for linkage analysis was an age specific (within 10-year age groups) z-score for the natural logarithm of the ratio of WMH to TCV. This z-score was based on 2230 individuals after excluding 26 participants with neurological conditions other than stroke and 3 individuals whose ages were out of range. Variance component linkage analysis included 747 individuals (mean age=62.16±12.43 years) with both magnetic resonance measure and genotype information in 237 families. Mean percent WMH to TCV was 0.098±0.175 with a range of 0.00025{\%} to 1.37{\%} in the linkage analysis subjects. Results - A maximum multipoint logarithm of the odds (LOD) score=3.69, which indicates significant evidence of linkage, was observed at 4 cM on chromosome 4. A suggestive peak with LOD=1.78 was observed at 95 cM on chromosome 17. Conclusion - We have significant evidence that a gene influencing WMH volume is located on chromosome 4 of the human genome.",
keywords = "Aging, Cerebrovascular disorders, Linkage (genetics)",
author = "DeStefano, {Anita L.} and Atwood, {Larry D.} and Massaro, {Joseph M.} and Nancy Heard-Costa and Alexa Beiser and Rhoda Au and Wolf, {Philip A.} and Charles DeCarli",
year = "2006",
month = "1",
doi = "10.1161/01.STR.0000196987.68770.b3",
language = "English (US)",
volume = "37",
pages = "77--81",
journal = "Stroke",
issn = "0039-2499",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

TY - JOUR

T1 - Genome-wide scan for white matter hyperintensity

T2 - The framingham heart study

AU - DeStefano, Anita L.

AU - Atwood, Larry D.

AU - Massaro, Joseph M.

AU - Heard-Costa, Nancy

AU - Beiser, Alexa

AU - Au, Rhoda

AU - Wolf, Philip A.

AU - DeCarli, Charles

PY - 2006/1

Y1 - 2006/1

N2 - Background and Purpose - White matter hyperintensity (WMH) volume is associated with aging and cerebrovascular disease and has been demonstrated to have a high heritability in the Framingham Heart Study as well as in other studies. We performed a genome-wide linkage analysis to identify chromosomal regions that may harbor genes influencing WMH in a family-based sample of the Framingham Heart Study. Methods - Brain magnetic resonance scans were performed, and WMH and total cranial volume (TCV) were quantified as previously described on 2259 cohort and offspring participants. The outcome used for linkage analysis was an age specific (within 10-year age groups) z-score for the natural logarithm of the ratio of WMH to TCV. This z-score was based on 2230 individuals after excluding 26 participants with neurological conditions other than stroke and 3 individuals whose ages were out of range. Variance component linkage analysis included 747 individuals (mean age=62.16±12.43 years) with both magnetic resonance measure and genotype information in 237 families. Mean percent WMH to TCV was 0.098±0.175 with a range of 0.00025% to 1.37% in the linkage analysis subjects. Results - A maximum multipoint logarithm of the odds (LOD) score=3.69, which indicates significant evidence of linkage, was observed at 4 cM on chromosome 4. A suggestive peak with LOD=1.78 was observed at 95 cM on chromosome 17. Conclusion - We have significant evidence that a gene influencing WMH volume is located on chromosome 4 of the human genome.

AB - Background and Purpose - White matter hyperintensity (WMH) volume is associated with aging and cerebrovascular disease and has been demonstrated to have a high heritability in the Framingham Heart Study as well as in other studies. We performed a genome-wide linkage analysis to identify chromosomal regions that may harbor genes influencing WMH in a family-based sample of the Framingham Heart Study. Methods - Brain magnetic resonance scans were performed, and WMH and total cranial volume (TCV) were quantified as previously described on 2259 cohort and offspring participants. The outcome used for linkage analysis was an age specific (within 10-year age groups) z-score for the natural logarithm of the ratio of WMH to TCV. This z-score was based on 2230 individuals after excluding 26 participants with neurological conditions other than stroke and 3 individuals whose ages were out of range. Variance component linkage analysis included 747 individuals (mean age=62.16±12.43 years) with both magnetic resonance measure and genotype information in 237 families. Mean percent WMH to TCV was 0.098±0.175 with a range of 0.00025% to 1.37% in the linkage analysis subjects. Results - A maximum multipoint logarithm of the odds (LOD) score=3.69, which indicates significant evidence of linkage, was observed at 4 cM on chromosome 4. A suggestive peak with LOD=1.78 was observed at 95 cM on chromosome 17. Conclusion - We have significant evidence that a gene influencing WMH volume is located on chromosome 4 of the human genome.

KW - Aging

KW - Cerebrovascular disorders

KW - Linkage (genetics)

UR - http://www.scopus.com/inward/record.url?scp=33644876583&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33644876583&partnerID=8YFLogxK

U2 - 10.1161/01.STR.0000196987.68770.b3

DO - 10.1161/01.STR.0000196987.68770.b3

M3 - Article

C2 - 16322484

AN - SCOPUS:33644876583

VL - 37

SP - 77

EP - 81

JO - Stroke

JF - Stroke

SN - 0039-2499

IS - 1

ER -