Genome wide association study identifies variants in NBEA associated with migraine in bipolar disorder

Jacobsen, Kaya Kvarme; Nievergelt, Caroline M.; Zayats, Tetyana; Greenwood, Tiffany A.; Anttila, Verneri; Akiskal, Hagop S.; Haavik, Jan; Fasmer, Ole Bernt; Kelsoe, John R.; Johansson, Stefan; Oedegaard, Ketil J.; Liu, Chengyu; Wedenoja, Juho; Kaunisto, Mari A.; Heikkilä, Kauko; Kaprio, Jaakko; Wessman, Maija; Kallela, Mikko; Färkkilä, Markus; Artto, Ville; Eriksson, Johan G.; Palotie, Aarno; Daly, Mark J.

doi:10.1016/j.jad.2014.10.004

Cited by 16 publications

(10 citation statements)

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“…Recently, the SNP rs1160720 (near NBEA on 13q13.3) was found to be significantly associated with comorbid bipolar disorder and migraine ( p = 2.97 × 10 −8 ) by comparing 460 bipolar migraineurs and 914 bipolar patients without migraine (107). Although bipolar disorder shares signs and symptoms with depression, association of this SNP was not observed ( p > 0.05) in the 2013 Psychiatric Genomics Consortium (PGC) MDD GWAS (102) (https://www.med.unc.edu/pgc/files/resultfiles/pgc.mdd.2012-04.zip) and the 2013 International Headache Genetics Consortium (IHGC) migraine GWAS (101).…”

Section: Genome-wide Association Studiesmentioning

confidence: 99%

Genetic epidemiology of migraine and depression

et al. 2016

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Epidemiological findings indicate that there is a bidirectional relationship between migraine and depression, with one disorder increasing the risk for the other and vice versa, suggesting shared biological mechanisms. Twin and family studies indicate that this bidirectional relationship can be explained, at least partly, by shared underlying genetically determined disease mechanisms. Although no genes have been robustly associated with the aetiology of both migraine and depression, genes from serotonergic, dopaminergic and GABAergic systems together with variants in the MTHFR and BDNF genes remain strong candidates.

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Section: Genome-wide Association Studiesmentioning

confidence: 99%

Genetic epidemiology of migraine and depression

et al. 2016

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“…In a study using cluster analysis for patients with chronic migraine, patients with high levels of affective temperamental dysregulation showed a higher risk of suicidal behavior [ 24 ]. Recent studies also supported genome wide association between migraine and bipolar disorder, therefore, it is important to identify manageable psychiatric comorbidities for effective treatment and improving life quality among migraineurs [ 25 , 26 ]. However, an association between SCD and comorbid symptoms or pain severity has not yet been investigated with relevant cognitive tests among patients with migraine.…”

Section: Introductionmentioning

confidence: 99%

Subjective cognitive decline in patients with migraine and its relationship with depression, anxiety, and sleep quality

2017

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BackgroundCognitive decline is a major concern in patients with migraine. Depression, anxiety, and/or poor sleep quality are well-known comorbidities of migraine, but available evidence on the subjective cognitive decline (SCD) is limited. This study aimed to investigate the presence and frequency of SCD and its relationship with anxiety, depression and sleep quality in patients with migraine.MethodsWe enrolled patients with migraine who scored within the normal range of the Korean-Mini Mental State Examination and the Korean-Montreal Cognitive Assessment. Using the Subjective Cognitive Decline Questionnaire (SCD-Q), participants with ≥7 were assigned to the SCD group. The Headache Impact Test-6, Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, and Pittsburgh Sleep Quality Index were used and analyzed between the two groups.ResultsA total of 188 patients with migraine, aged 38.1 ± 9.9 years, were enrolled. The mean SCD-Q score was 6.5 ± 5.5, and 44.7% of participants were identified as SCD. Migraineurs with SCD reported higher headache pain intensity and headache impact, as well as greater prevalence of anxiety, depression, reduced quality of sleep, and shorter sleep duration during weekdays compared to migraineurs without SCD. There were no significant differences in terms of age, sex, migraine type (chronic/episodic), medication, or sleep duration during weekends between the two groups. Upon multivariate logistic analysis adjusted for age, sex, headache characteristics, and psychological variables, depression was associated with increased risk of SCD (Odds ratio 1.31, 95% confidence interval 1.16–1.49) and sleep duration during weekdays was associated with decreased risk of SCD (Odds ratio 0.66, 95% confidence interval 0.44–0.97).ConclusionsA non-negligible number of patients with migraine complained of SCD. Depression and short sleep duration during weekdays were related to SCD among adult migraineurs.

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“…Among our other findings are loci at 13q13.3, and 9q22.1. The 13q13.3 lead SNP is located within an intron of neurobeachin ( NBEA ), a synaptic scaffolding protein associated with autism (Castermans et al, ) and migraine in bipolar disorder (Jacobsen et al, ). Little is known about spermatogenesis‐associated protein 31C2 ( SPATA31C2 ), the proximal gene at the 9q22.1 locus.…”

Section: Discussionmentioning

confidence: 99%

Genome‐wide interaction studies identify sex‐specific risk alleles for nonsyndromic orofacial clefts

Carlson

Nidey

Butali

et al. 2018

Genetic Epidemiology

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Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is the most common craniofacial birth defect in humans and is notable for its apparent sexual dimorphism where approximately twice as many males are affected as females. The sources of this disparity are largely unknown, but interactions between genetic and sex effects are likely contributors. We examined gene-by-sex (G x S) interactions in a worldwide sample of 2,142 NSCL/P cases and 1,700 controls recruited from 13 countries. First, we performed genome-wide joint tests of the genetic (G) and G x S effects genome-wide using logistic regression assuming an additive genetic model and adjusting for 18 principal components of ancestry. We further interrogated loci with suggestive results from the joint test (p < 1.00 × 10−5) by examining the G x S effects from the same model. Out of the 133 loci with suggestive results (p < 1.00 × 10−5) for the joint test, we observed one genome-wide significant G x S effect in the 10q21 locus (rs72804706; p = 6.69 × 10−9; OR = 2.62 [1.89, 3.62]) and 16 suggestive G x S effects. At the intergenic 10q21 locus, the risk of NSCL/P is estimated to increase with additional copies of the minor allele for females, but the opposite effect for males. Our observation that the impact of genetic variants on NSCL/P risk differs for males and females may further our understanding of the genetic architecture of NSCL/P and the sex differences underlying clefts and other birth defects.

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Genome wide association study identifies variants in NBEA associated with migraine in bipolar disorder

Cited by 16 publications

References 62 publications

Genetic epidemiology of migraine and depression

Genetic epidemiology of migraine and depression

Subjective cognitive decline in patients with migraine and its relationship with depression, anxiety, and sleep quality

Genome‐wide interaction studies identify sex‐specific risk alleles for nonsyndromic orofacial clefts

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