Is the genetic liability in multifactorial disorders higher in concordant than discordant monozygotic twin pairs? A population-based family twin study of migraine without aura.

Abstract

Migraine without aura (MO) is a multifactorial disorder. Expression of a disorder with multifactorial inheritance depends on the genetic liability and on environmental factors. A high liability is reflected by a high frequency of affected relatives. We have previously shown that monozygotic (MZ) twin pairs have a significant higher concordance of MO than dizygotic twin pairs. The incomplete concordance among MZ twin pairs may be due to a lower genetic liability among discordant than concordant MZ twin pairs. The present study analysed the genetic liability in MZ twin pairs concordant and discordant for MO by the population-relative risk of MO among parents and siblings. The twin pairs were from the population-based Danish Twin Register. First-degree relatives of 29 concordant and 34 discordant MZ twin pairs were blindly telephone interviewed by a physician. The participation rate of the eligible first-degree relatives was 96%. The population-relative risk of MO among parents and siblings was 2.73 (2.39-3.06) in concordant and 2.37 (2.03-2.71) in discordant MZ twin pairs. The relative risk of MO was significantly higher in female first-degree relatives of concordant than of discordant MZ male and female twin pairs. An opposite effect was observed in male first-degree relatives, although this was not significant for male first-degree relatives of female MZ twin pairs. The present study found no statistically significant difference in genetic liability to MO among concordant and discordant MZ twin pairs. However, a difference in genetic liability among MZ and DZ twin pairs is anticipated to be small. Thus, it may be possible to show the effect in a larger study population or by investigating a more frequent trait than MO.