Dissecting the shared genetic basis of migraine and mental disorders using novel statistical tools

作者：Shahram Bahrami, Guy Hindley, Bendik S. Winsvold, Kevin S. O’Connell, Oleksandr Frei, Alexey Shadrin, Weiqiu Cheng, Francesco Bettella, Linn Rødevand, Ketil Joachim Ødegaard, Chun Chieh Fan, Matti Pirinen, Heidi Hautakangas, HUNT All-In Headache, Amy E. Martinsen, Anne Heidi Skogholt, Ben Brumpton, Cristen J. Willer, Erling Tronvik, Espen Saxhaug Kristoffersen, John‐Anker Zwart, Jonas B. Nielsen, Knut Hagen, Kristian Bernhard Nilsen, Kristian Hveem, Lars Jacob Stovner, Lars G. Fritsche, Laurent F. Thomas, Linda M. Pedersen, Maiken E. Gabrielsen, Marianne Bakke Johnsen, Marie Udnesseter Lie, Oddgeir L. Holmen, Sigrid Børte, Synne Øien Stensland, Wei Zhou, Anders M. Dale, Srdjan Djurovic, Olav B. Smeland, Ole A. Andreassen · 发表于：Brain · 年份：2021 · DOI：10.1093/brain/awab267 · 被引用次数：68 · 研究领域：Migraine and Headache Studies、Suicide and Self-Harm Studies、Neuroscience of respiration and sleep

Migraine is three times more prevalent in people with bipolar disorder or depression. The relationship between schizophrenia and migraine is less certain although glutamatergic and serotonergic neurotransmission are implicated in both. A shared genetic basis to migraine and mental disorders has been suggested but previous studies have reported weak or non-significant genetic correlations and five shared risk loci. Using the largest samples to date and novel statistical tools, we aimed to determine the extent to which migraine's polygenic architecture overlaps with bipolar disorder, depression and schizophrenia beyond genetic correlation, and to identify shared genetic loci. Summary statistics from genome-wide association studies were acquired from large-scale consortia for migraine (n cases = 59 674; n controls = 316 078), bipolar disorder (n cases = 20 352; n controls = 31 358), depression (n cases = 170 756; n controls = 328 443) and schizophrenia (n cases = 40 675, n controls = 64 643). We applied the bivariate causal mixture model to estimate the number of disorder-influencing variants shared between migraine and each mental disorder, and the conditional/conjunctional false discovery rate method to identify shared loci. Loci were functionally characterized to provide biological insights. Univariate MiXeR analysis revealed that migraine was substantially less polygenic (2.8 K disorder-influencing variants) compared to mental disorders (8100-12 300 disorder-influencing vari...