Heritability of circle of Willis variations in families with intracranial aneurysms

Mayte Sánchez Van Kammen, Charles J. Moomaw, Irene C. Van Der Schaaf, Robert D. Brown, Daniel Woo, Joseph P. Broderick, Jason Mackey, Gabriël J.E. Rinkel, John Huston, Ynte M. Ruigrok

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background Intracranial aneurysms more often occur in the same arterial territory within families. Several aneurysm locations are associated with specific circle of Willis variations. We investigated whether the same circle of Willis variations are more likely to occur in first-degree relatives than in unrelated individuals. Methods We assessed four circle of Willis variations (classical, A1-asymmetry, incomplete posterior communicating artery and fetal circulation) in two independent groups of families with familial aneurysms and 2 first-degree relatives with circle of Willis imaging on MRA/ CTA. In each (index) family we determined the proportion of first-degree relatives with the same circle of Willis variation as the proband and compared it to the proportion of first-degree relatives of a randomly selected unrelated (comparison) family who had the same circle of Willis variation as the index family’s proband. Concordance in index families and comparison families was compared with a conditional logistic events/trials model. The analysis was simulated 1001 times; we report the median concordances, odds ratios (ORs), and 95% confidence intervals (95%CI). The groups were analysed separately and together by meta-analysis. Results We found a higher overall concordance in circle of Willis configuration in index families than in comparison families (meta-analysis, 244 families: OR 2.2, 95%CI 1.6–3.0) mostly attributable to a higher concordance in incomplete posterior communicating artery (meta-analysis: OR 2.8, 95%CI 1.8–4.3). No association was found for the other three circle of Willis variations. Conclusions In two independent groups of families with familial aneurysms, the incomplete PcomA variation occurred more often within than between families suggesting heritability of this circle of Willis variation. Further studies should investigate genetic variants associated with circle of Willis formation.

Original languageEnglish (US)
Article numbere0191974
JournalPLoS One
Volume13
Issue number1
DOIs
StatePublished - Jan 1 2018

Fingerprint

Circle of Willis
aneurysm
Intracranial Aneurysm
Logistics
heritability
meta-analysis
odds ratio
Imaging techniques
confidence interval
arteries
Aneurysm
Meta-Analysis
Odds Ratio
Confidence Intervals
image analysis
Arteries

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Van Kammen, M. S., Moomaw, C. J., Van Der Schaaf, I. C., Brown, R. D., Woo, D., Broderick, J. P., ... Ruigrok, Y. M. (2018). Heritability of circle of Willis variations in families with intracranial aneurysms. PLoS One, 13(1), [e0191974]. https://doi.org/10.1371/journal.pone.0191974

Heritability of circle of Willis variations in families with intracranial aneurysms. / Van Kammen, Mayte Sánchez; Moomaw, Charles J.; Van Der Schaaf, Irene C.; Brown, Robert D.; Woo, Daniel; Broderick, Joseph P.; Mackey, Jason; Rinkel, Gabriël J.E.; Huston, John; Ruigrok, Ynte M.

In: PLoS One, Vol. 13, No. 1, e0191974, 01.01.2018.

Research output: Contribution to journalArticle

Van Kammen, MS, Moomaw, CJ, Van Der Schaaf, IC, Brown, RD, Woo, D, Broderick, JP, Mackey, J, Rinkel, GJE, Huston, J & Ruigrok, YM 2018, 'Heritability of circle of Willis variations in families with intracranial aneurysms', PLoS One, vol. 13, no. 1, e0191974. https://doi.org/10.1371/journal.pone.0191974
Van Kammen MS, Moomaw CJ, Van Der Schaaf IC, Brown RD, Woo D, Broderick JP et al. Heritability of circle of Willis variations in families with intracranial aneurysms. PLoS One. 2018 Jan 1;13(1). e0191974. https://doi.org/10.1371/journal.pone.0191974
Van Kammen, Mayte Sánchez ; Moomaw, Charles J. ; Van Der Schaaf, Irene C. ; Brown, Robert D. ; Woo, Daniel ; Broderick, Joseph P. ; Mackey, Jason ; Rinkel, Gabriël J.E. ; Huston, John ; Ruigrok, Ynte M. / Heritability of circle of Willis variations in families with intracranial aneurysms. In: PLoS One. 2018 ; Vol. 13, No. 1.
@article{da82ebb0c2a743c3be0f8a90dc17a555,
title = "Heritability of circle of Willis variations in families with intracranial aneurysms",
abstract = "Background Intracranial aneurysms more often occur in the same arterial territory within families. Several aneurysm locations are associated with specific circle of Willis variations. We investigated whether the same circle of Willis variations are more likely to occur in first-degree relatives than in unrelated individuals. Methods We assessed four circle of Willis variations (classical, A1-asymmetry, incomplete posterior communicating artery and fetal circulation) in two independent groups of families with familial aneurysms and 2 first-degree relatives with circle of Willis imaging on MRA/ CTA. In each (index) family we determined the proportion of first-degree relatives with the same circle of Willis variation as the proband and compared it to the proportion of first-degree relatives of a randomly selected unrelated (comparison) family who had the same circle of Willis variation as the index family’s proband. Concordance in index families and comparison families was compared with a conditional logistic events/trials model. The analysis was simulated 1001 times; we report the median concordances, odds ratios (ORs), and 95{\%} confidence intervals (95{\%}CI). The groups were analysed separately and together by meta-analysis. Results We found a higher overall concordance in circle of Willis configuration in index families than in comparison families (meta-analysis, 244 families: OR 2.2, 95{\%}CI 1.6–3.0) mostly attributable to a higher concordance in incomplete posterior communicating artery (meta-analysis: OR 2.8, 95{\%}CI 1.8–4.3). No association was found for the other three circle of Willis variations. Conclusions In two independent groups of families with familial aneurysms, the incomplete PcomA variation occurred more often within than between families suggesting heritability of this circle of Willis variation. Further studies should investigate genetic variants associated with circle of Willis formation.",
author = "{Van Kammen}, {Mayte S{\'a}nchez} and Moomaw, {Charles J.} and {Van Der Schaaf}, {Irene C.} and Brown, {Robert D.} and Daniel Woo and Broderick, {Joseph P.} and Jason Mackey and Rinkel, {Gabri{\"e}l J.E.} and John Huston and Ruigrok, {Ynte M.}",
year = "2018",
month = "1",
day = "1",
doi = "10.1371/journal.pone.0191974",
language = "English (US)",
volume = "13",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "1",

}

TY - JOUR

T1 - Heritability of circle of Willis variations in families with intracranial aneurysms

AU - Van Kammen, Mayte Sánchez

AU - Moomaw, Charles J.

AU - Van Der Schaaf, Irene C.

AU - Brown, Robert D.

AU - Woo, Daniel

AU - Broderick, Joseph P.

AU - Mackey, Jason

AU - Rinkel, Gabriël J.E.

AU - Huston, John

AU - Ruigrok, Ynte M.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background Intracranial aneurysms more often occur in the same arterial territory within families. Several aneurysm locations are associated with specific circle of Willis variations. We investigated whether the same circle of Willis variations are more likely to occur in first-degree relatives than in unrelated individuals. Methods We assessed four circle of Willis variations (classical, A1-asymmetry, incomplete posterior communicating artery and fetal circulation) in two independent groups of families with familial aneurysms and 2 first-degree relatives with circle of Willis imaging on MRA/ CTA. In each (index) family we determined the proportion of first-degree relatives with the same circle of Willis variation as the proband and compared it to the proportion of first-degree relatives of a randomly selected unrelated (comparison) family who had the same circle of Willis variation as the index family’s proband. Concordance in index families and comparison families was compared with a conditional logistic events/trials model. The analysis was simulated 1001 times; we report the median concordances, odds ratios (ORs), and 95% confidence intervals (95%CI). The groups were analysed separately and together by meta-analysis. Results We found a higher overall concordance in circle of Willis configuration in index families than in comparison families (meta-analysis, 244 families: OR 2.2, 95%CI 1.6–3.0) mostly attributable to a higher concordance in incomplete posterior communicating artery (meta-analysis: OR 2.8, 95%CI 1.8–4.3). No association was found for the other three circle of Willis variations. Conclusions In two independent groups of families with familial aneurysms, the incomplete PcomA variation occurred more often within than between families suggesting heritability of this circle of Willis variation. Further studies should investigate genetic variants associated with circle of Willis formation.

AB - Background Intracranial aneurysms more often occur in the same arterial territory within families. Several aneurysm locations are associated with specific circle of Willis variations. We investigated whether the same circle of Willis variations are more likely to occur in first-degree relatives than in unrelated individuals. Methods We assessed four circle of Willis variations (classical, A1-asymmetry, incomplete posterior communicating artery and fetal circulation) in two independent groups of families with familial aneurysms and 2 first-degree relatives with circle of Willis imaging on MRA/ CTA. In each (index) family we determined the proportion of first-degree relatives with the same circle of Willis variation as the proband and compared it to the proportion of first-degree relatives of a randomly selected unrelated (comparison) family who had the same circle of Willis variation as the index family’s proband. Concordance in index families and comparison families was compared with a conditional logistic events/trials model. The analysis was simulated 1001 times; we report the median concordances, odds ratios (ORs), and 95% confidence intervals (95%CI). The groups were analysed separately and together by meta-analysis. Results We found a higher overall concordance in circle of Willis configuration in index families than in comparison families (meta-analysis, 244 families: OR 2.2, 95%CI 1.6–3.0) mostly attributable to a higher concordance in incomplete posterior communicating artery (meta-analysis: OR 2.8, 95%CI 1.8–4.3). No association was found for the other three circle of Willis variations. Conclusions In two independent groups of families with familial aneurysms, the incomplete PcomA variation occurred more often within than between families suggesting heritability of this circle of Willis variation. Further studies should investigate genetic variants associated with circle of Willis formation.

UR - http://www.scopus.com/inward/record.url?scp=85041127983&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85041127983&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0191974

DO - 10.1371/journal.pone.0191974

M3 - Article

VL - 13

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 1

M1 - e0191974

ER -