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Familial Aggregation of Migraine and Depression: Insights From a Large Australian Twin Sample.

ABSTRACT: This research examined the familial aggregation of migraine, depression, and their co-occurrence.Diagnoses of migraine and depression were determined in a sample of 5,319 Australian twins. Migraine was diagnosed by either self-report, the ID migraine™ Screener, or International Headache Society (IHS) criteria. Depression was defined by fulfilling either major depressive disorder (MDD) or minor depressive disorder (MiDD) based on the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria. The relative risks (RR) for migraine and depression were estimated in co-twins of twin probands reporting migraine or depression to evaluate their familial aggregation and co-occurrence.An increased RR of both migraine and depression in co-twins of probands with the same trait was observed, with significantly higher estimates within monozygotic (MZ) twin pairs compared to dizygotic (DZ) twin pairs. For cross-trait analysis, the RR for migraine in co-twins of probands reporting depression was 1.36 (95% CI: 1.24-1.48) in MZ pairs and 1.04 (95% CI: 0.95-1.14) in DZ pairs; and the RR for depression in co-twins of probands reporting migraine was 1.26 (95% CI: 1.14-1.38) in MZ pairs and 1.02 (95% CI: 0.94-1.11) in DZ pairs. The RR for strict IHS migraine in co-twins of probands reporting MDD was 2.23 (95% CI: 1.81-2.75) in MZ pairs and 1.55 (95% CI: 1.34-1.79) in DZ pairs; and the RR for MDD in co-twins of probands reporting IHS migraine was 1.35 (95% CI: 1.13-1.62) in MZ pairs and 1.06 (95% CI: 0.93-1.22) in DZ pairs.We observed significant evidence for a genetic contribution to familial aggregation of migraine and depression. Our findings suggest a bi-directional association between migraine and depression, with an increased risk for depression in relatives of probands reporting migraine, and vice versa. However, the observed risk for migraine in relatives of probands reporting depression was considerably higher than the reverse. These results add further support to previous studies suggesting that patients with comorbid migraine and depression are genetically more similar to patients with only depression than patients with only migraine.

SUBMITTER: Yang Y

PROVIDER: S-EPMC5466692 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Familial Aggregation of Migraine and Depression: Insights From a Large Australian Twin Sample.

Yang Yuanhao Y Zhao Huiying H Heath Andrew C AC Madden Pamela A F PA Martin Nicholas G NG Nyholt Dale R DR

Twin research and human genetics : the official journal of the International Society for Twin Studies 20160606 4

<h4>Objectives</h4>This research examined the familial aggregation of migraine, depression, and their co-occurrence.<h4>Methods</h4>Diagnoses of migraine and depression were determined in a sample of 5,319 Australian twins. Migraine was diagnosed by either self-report, the ID migraine™ Screener, or International Headache Society (IHS) criteria. Depression was defined by fulfilling either major depressive disorder (MDD) or minor depressive disorder (MiDD) based on the Diagnostic and Statistical M ...[more]

PMID: 27263615

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Project description:Background: Vestibular migraine (VM) is complex disorder consisting of episodes of migraine and vertigo with an estimated prevalence of 1-3%. As migraine, it is considered that VM has genetic predisposition; however, evidence to support a genetic contribution has not been critically appraised. Objective: The aim of this systematic review is to assess available evidence in scientific publications to determine the role of inheritance in VM. Methods: After performing the quality assessment of the retrieved records, 31 studies were included (24 epidemiological reports and 7 genetic association studies in families or case-control in candidate genes). We gathered data about prevalence of VM in different populations and in families, and also about the genetic findings reported. In addition, other variables were considered to assess the heritability of VM, such as the ancestry, the age of onset or the familial history of vertigo and migraine. Results: The estimated prevalence of VM was different between black (3.13%), white (2.64%) and Asian (1.07%) ethnicities. The reported prevalence of VM in migraine patients is higher in European countries (21%) than in Asian countries (10%). Moreover, the prevalence of the migraine-vertigo association in families is 4-10 times higher than the prevalence reported in the general population (sibling recurrence risk ratio λs = 4.31-10.42). We also found that the age of onset is lower in patients with simultaneous onset of symptoms and in those who have familial history for migraine and/or vertigo, suggesting anticipation. Although some genetic studies have reported few allelic variants associated to MV, replication studies are needed to validate these results. Conclusions: The available evidence to support heritability in VM is limited. Variability in prevalence depending on ethnicity and geographic location suggests a combined genetic and environmental contribution to VM. However, the familial aggregation observed in VM support genetic and shared familial environmental effects that remarks the necessity of twins and adoptees-based epidemiological studies to estimate its heritability.

Project description:BackgroundPrevious epidemiological and other studies have shown an association between major depressive disorder (MDD) and migraine. However, the causal relationship between them remains unclear. Therefore, this study aimed to investigate the causal relationship between MDD and migraine using a bidirectional, two-sample Mendelian randomization (MR) approach.MethodsData on MDD and migraine, including subtypes with aura migraine (MA) and without aura migraine (MO), were gathered from a publicly available genome-wide association study (GWAS). Single nucleotide polymorphisms (SNPs) utilized as instrumental variables (IVs) were then screened by adjusting the intensity of the connection and removing linkage disequilibrium. To explore causal effects, inverse variance weighting (IVW) was used as the primary analysis method, with weighted median, MR-Egger, simple mode, and weighted mode used as supplementary analytic methods. Furthermore, heterogeneity and pleiotropy tests were carried out. Cochran's Q-test with IVW and MR-Egger was used to assess heterogeneity. Pleiotropy testing was carried out using the MR-Egger intercept and MR-PRESSO analysis methods. A leave-one-out analysis was also used to evaluate the stability of the findings. Finally, we used migraine (MA and MO) levels to deduce reverse causality with MDD risk.ResultsRandom effects IVW results were (MDD-Migraine: odds ratio (OR), 1.606, 95% confidence interval (CI), 1.324-1.949, p = 1.52E-06; MDD-MA: OR, 1.400, 95%CI, 1.067-1.8378, p = 0.015; MDD-MO: OR, 1.814, 95%CI, 1.277-2.578, p = 0.0008), indicating a causal relationship between MDD levels and increased risk of migraine (including MA and MO). In the inverse MR analysis, the findings were all negative, while in sensitivity analyses, the results were robust except for the study of MA with MDD.ConclusionOur study confirms a causal relationship between MDD levels and increased risk of migraine, MA, and MO. There was little evidence in the reverse MR analysis to suggest a causal genetic relationship between migraine (MA and MO) and MDD risk levels.

Dataset Information

Familial Aggregation of Migraine and Depression: Insights From a Large Australian Twin Sample.

Publications

Familial Aggregation of Migraine and Depression: Insights From a Large Australian Twin Sample.

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