Evidence for genetic variance in white matter hyperintensity volume in normal elderly male twins

Dorit Carmelli, Charles DeCarli, Gary E. Swan, Lisa M. Jack, Terry Reed, Philip A. Wolf, Bruce L. Miller

Research output: Contribution to journalArticle

258 Citations (Scopus)

Abstract

Background and Purpose - White matter hyperintensities (WMHs), as detected by MRI, are common among the elderly and are frequently interpreted as representing a subclinical form of ischemic brain damage. We used volumetric MR techniques to investigate the contribution of genes and the environment to measures of brain morphology in a sample of community dwelling elderly male twins. Methods - Brain MR (1.5 T) scans were obtained from 74 monozygotic (MZ) and 71 dizygotic (DZ), white, male, World War II veteran twins born in the United States and age 68 to 79 when scanned. MR quantification used a previously published semiautomated segmentation algorithm to segment brain images into total brain, cerebrospinal fluid (CSF), and WMH volumes. Twin pair covariances were computed for each measure, and structural equation genetic models were fitted to these data. Results - Total cranial, brain parenchyma, CSF, and WMH volumes were highly correlated in MZ pairs, and correlations in MZ pairs were significantly greater than those in DZ pairs. Structural equation modeling indicated heritabilities of 91%, 92%, and 73%, respectively, for total cranial, brain parenchyma, and WMH volumes. Correction for age and head size reduced the heritability of brain parenchyma to 62% (95% confidence interval, 56% to 68%) and the heritability of WMH volume to 71% (95% confidence interval, 66% to 76%). Proband concordance rates for large amounts of WMH were 61% in MZ paris and 38% in DZ pairs, compared with a prevalence of 15% in the entire sample. Conclusions - This study is the first to quantify the relative contribution of genetic and individual environmental influences to measures of brain morphology in the elderly.

Original languageEnglish (US)
Pages (from-to)1177-1181
Number of pages5
JournalStroke
Volume29
Issue number6
StatePublished - Jun 1998
Externally publishedYes

Fingerprint

Brain
Cerebrospinal Fluid
Confidence Intervals
Independent Living
White Matter
World War II
Genetic Models
Paris
Veterans
Head
Genes

Keywords

  • Aging
  • Genetics
  • Magnetic resonance imaging
  • White matter

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Neuroscience(all)

Cite this

Carmelli, D., DeCarli, C., Swan, G. E., Jack, L. M., Reed, T., Wolf, P. A., & Miller, B. L. (1998). Evidence for genetic variance in white matter hyperintensity volume in normal elderly male twins. Stroke, 29(6), 1177-1181.

Evidence for genetic variance in white matter hyperintensity volume in normal elderly male twins. / Carmelli, Dorit; DeCarli, Charles; Swan, Gary E.; Jack, Lisa M.; Reed, Terry; Wolf, Philip A.; Miller, Bruce L.

In: Stroke, Vol. 29, No. 6, 06.1998, p. 1177-1181.

Research output: Contribution to journalArticle

Carmelli, D, DeCarli, C, Swan, GE, Jack, LM, Reed, T, Wolf, PA & Miller, BL 1998, 'Evidence for genetic variance in white matter hyperintensity volume in normal elderly male twins', Stroke, vol. 29, no. 6, pp. 1177-1181.
Carmelli D, DeCarli C, Swan GE, Jack LM, Reed T, Wolf PA et al. Evidence for genetic variance in white matter hyperintensity volume in normal elderly male twins. Stroke. 1998 Jun;29(6):1177-1181.
Carmelli, Dorit ; DeCarli, Charles ; Swan, Gary E. ; Jack, Lisa M. ; Reed, Terry ; Wolf, Philip A. ; Miller, Bruce L. / Evidence for genetic variance in white matter hyperintensity volume in normal elderly male twins. In: Stroke. 1998 ; Vol. 29, No. 6. pp. 1177-1181.
@article{244caa3231334cffa40b9407bd334db5,
title = "Evidence for genetic variance in white matter hyperintensity volume in normal elderly male twins",
abstract = "Background and Purpose - White matter hyperintensities (WMHs), as detected by MRI, are common among the elderly and are frequently interpreted as representing a subclinical form of ischemic brain damage. We used volumetric MR techniques to investigate the contribution of genes and the environment to measures of brain morphology in a sample of community dwelling elderly male twins. Methods - Brain MR (1.5 T) scans were obtained from 74 monozygotic (MZ) and 71 dizygotic (DZ), white, male, World War II veteran twins born in the United States and age 68 to 79 when scanned. MR quantification used a previously published semiautomated segmentation algorithm to segment brain images into total brain, cerebrospinal fluid (CSF), and WMH volumes. Twin pair covariances were computed for each measure, and structural equation genetic models were fitted to these data. Results - Total cranial, brain parenchyma, CSF, and WMH volumes were highly correlated in MZ pairs, and correlations in MZ pairs were significantly greater than those in DZ pairs. Structural equation modeling indicated heritabilities of 91{\%}, 92{\%}, and 73{\%}, respectively, for total cranial, brain parenchyma, and WMH volumes. Correction for age and head size reduced the heritability of brain parenchyma to 62{\%} (95{\%} confidence interval, 56{\%} to 68{\%}) and the heritability of WMH volume to 71{\%} (95{\%} confidence interval, 66{\%} to 76{\%}). Proband concordance rates for large amounts of WMH were 61{\%} in MZ paris and 38{\%} in DZ pairs, compared with a prevalence of 15{\%} in the entire sample. Conclusions - This study is the first to quantify the relative contribution of genetic and individual environmental influences to measures of brain morphology in the elderly.",
keywords = "Aging, Genetics, Magnetic resonance imaging, White matter",
author = "Dorit Carmelli and Charles DeCarli and Swan, {Gary E.} and Jack, {Lisa M.} and Terry Reed and Wolf, {Philip A.} and Miller, {Bruce L.}",
year = "1998",
month = "6",
language = "English (US)",
volume = "29",
pages = "1177--1181",
journal = "Stroke",
issn = "0039-2499",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

TY - JOUR

T1 - Evidence for genetic variance in white matter hyperintensity volume in normal elderly male twins

AU - Carmelli, Dorit

AU - DeCarli, Charles

AU - Swan, Gary E.

AU - Jack, Lisa M.

AU - Reed, Terry

AU - Wolf, Philip A.

AU - Miller, Bruce L.

PY - 1998/6

Y1 - 1998/6

N2 - Background and Purpose - White matter hyperintensities (WMHs), as detected by MRI, are common among the elderly and are frequently interpreted as representing a subclinical form of ischemic brain damage. We used volumetric MR techniques to investigate the contribution of genes and the environment to measures of brain morphology in a sample of community dwelling elderly male twins. Methods - Brain MR (1.5 T) scans were obtained from 74 monozygotic (MZ) and 71 dizygotic (DZ), white, male, World War II veteran twins born in the United States and age 68 to 79 when scanned. MR quantification used a previously published semiautomated segmentation algorithm to segment brain images into total brain, cerebrospinal fluid (CSF), and WMH volumes. Twin pair covariances were computed for each measure, and structural equation genetic models were fitted to these data. Results - Total cranial, brain parenchyma, CSF, and WMH volumes were highly correlated in MZ pairs, and correlations in MZ pairs were significantly greater than those in DZ pairs. Structural equation modeling indicated heritabilities of 91%, 92%, and 73%, respectively, for total cranial, brain parenchyma, and WMH volumes. Correction for age and head size reduced the heritability of brain parenchyma to 62% (95% confidence interval, 56% to 68%) and the heritability of WMH volume to 71% (95% confidence interval, 66% to 76%). Proband concordance rates for large amounts of WMH were 61% in MZ paris and 38% in DZ pairs, compared with a prevalence of 15% in the entire sample. Conclusions - This study is the first to quantify the relative contribution of genetic and individual environmental influences to measures of brain morphology in the elderly.

AB - Background and Purpose - White matter hyperintensities (WMHs), as detected by MRI, are common among the elderly and are frequently interpreted as representing a subclinical form of ischemic brain damage. We used volumetric MR techniques to investigate the contribution of genes and the environment to measures of brain morphology in a sample of community dwelling elderly male twins. Methods - Brain MR (1.5 T) scans were obtained from 74 monozygotic (MZ) and 71 dizygotic (DZ), white, male, World War II veteran twins born in the United States and age 68 to 79 when scanned. MR quantification used a previously published semiautomated segmentation algorithm to segment brain images into total brain, cerebrospinal fluid (CSF), and WMH volumes. Twin pair covariances were computed for each measure, and structural equation genetic models were fitted to these data. Results - Total cranial, brain parenchyma, CSF, and WMH volumes were highly correlated in MZ pairs, and correlations in MZ pairs were significantly greater than those in DZ pairs. Structural equation modeling indicated heritabilities of 91%, 92%, and 73%, respectively, for total cranial, brain parenchyma, and WMH volumes. Correction for age and head size reduced the heritability of brain parenchyma to 62% (95% confidence interval, 56% to 68%) and the heritability of WMH volume to 71% (95% confidence interval, 66% to 76%). Proband concordance rates for large amounts of WMH were 61% in MZ paris and 38% in DZ pairs, compared with a prevalence of 15% in the entire sample. Conclusions - This study is the first to quantify the relative contribution of genetic and individual environmental influences to measures of brain morphology in the elderly.

KW - Aging

KW - Genetics

KW - Magnetic resonance imaging

KW - White matter

UR - http://www.scopus.com/inward/record.url?scp=0031778072&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031778072&partnerID=8YFLogxK

M3 - Article

C2 - 9626291

AN - SCOPUS:0031778072

VL - 29

SP - 1177

EP - 1181

JO - Stroke

JF - Stroke

SN - 0039-2499

IS - 6

ER -