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  • Oxford University Press (OUP)  (2)
  • Aromaa, Arpo J  (2)
  • 1
    Online Resource
    Online Resource
    Elucidating the relationship between migraine risk and brain structure using genetic data
    Oxford University Press (OUP) ; 2022
    In:  Brain Vol. 145, No. 9 ( 2022-09-14), p. 3214-3224
    Details
    In: Brain, Oxford University Press (OUP), Vol. 145, No. 9 ( 2022-09-14), p. 3214-3224
    Abstract: Migraine is a highly common and debilitating disorder that often affects individuals in their most productive years of life. Previous studies have identified both genetic variants and brain morphometry differences associated with migraine risk. However, the relationship between migraine and brain morphometry has not been examined on a genetic level, and the causal nature of the association between brain structure and migraine risk has not been determined. Using the largest available genome-wide association studies to date, we examined the genome-wide genetic overlap between migraine and intracranial volume, as well as the regional volumes of nine subcortical brain structures. We further focused the identification and biological annotation of genetic overlap between migraine and each brain structure on specific regions of the genome shared between migraine and brain structure. Finally, we examined whether the size of any of the examined brain regions causally increased migraine risk using a Mendelian randomization approach. We observed a significant genome-wide negative genetic correlation between migraine risk and intracranial volume (rG = −0.11, P = 1 × 10−3) but not with any subcortical region. However, we identified jointly associated regional genomic overlap between migraine and every brain structure. Gene enrichment in these shared genomic regions pointed to possible links with neuronal signalling and vascular regulation. Finally, we provide evidence of a possible causal relationship between smaller total brain, hippocampal and ventral diencephalon volume and increased migraine risk, as well as a causal relationship between increased risk of migraine and a larger volume of the amygdala. We leveraged the power of large genome-wide association studies to show evidence of shared genetic pathways that jointly influence migraine risk and several brain structures, suggesting that altered brain morphometry in individuals with high migraine risk may be genetically mediated. Further interrogation of these results showed support for the neurovascular hypothesis of migraine aetiology and shed light on potentially viable therapeutic targets.
    Type of Medium: Online Resource
    ISSN: 0006-8950 , 1460-2156
    URL: Article
    DOI: 10.1093/brain/awac105
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 1474117-9
    SSG: 12
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  • 2
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    Cross-trait analyses with migraine reveal widespread pleiotropy and suggest a vascular component to migraine headache
    Oxford University Press (OUP) ; 2020
    In:  International Journal of Epidemiology Vol. 49, No. 3 ( 2020-06-01), p. 1022-1031
    Details
    In: International Journal of Epidemiology, Oxford University Press (OUP), Vol. 49, No. 3 ( 2020-06-01), p. 1022-1031
    Abstract: Nearly a fifth of the world’s population suffer from migraine headache, yet risk factors for this disease are poorly characterized. Methods To further elucidate these factors, we conducted a genetic correlation analysis using cross-trait linkage disequilibrium (LD) score regression between migraine headache and 47 traits from the UK Biobank. We then tested for possible causality between these phenotypes and migraine, using Mendelian randomization. In addition, we attempted replication of our findings in an independent genome-wide association study (GWAS) when available. Results We report multiple phenotypes with genetic correlation (P  & lt; 1.06 × 10−3) with migraine, including heart disease, type 2 diabetes, lipid levels, blood pressure, autoimmune and psychiatric phenotypes. In particular, we find evidence that blood pressure directly contributes to migraine and explains a previously suggested causal relationship between calcium and migraine. Conclusions This is the largest genetic correlation analysis of migraine headache to date, both in terms of migraine GWAS sample size and the number of phenotypes tested. We find that migraine has a shared genetic basis with a large number of traits, indicating pervasive pleiotropy at migraine-associated loci.
    Type of Medium: Online Resource
    ISSN: 0300-5771 , 1464-3685
    URL: Article
    DOI: 10.1093/ije/dyaa050
    RVK:
    XF 4100
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 1494592-7
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