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Shared genetic basis for migraine and ischemic stroke: A genome-wide analysis of common variants.
Friday,2015-08-28 11:52 America/Los_Angeles — zdrager
| Title | Shared genetic basis for migraine and ischemic stroke: A genome-wide analysis of common variants. |
| Publication Type | Journal Article |
| Year of Publication | 2015 |
| Authors | Malik, R, Freilinger, T, Winsvold, BS, Anttila, V, Heiden, JVander, Traylor, M, de Vries, B, Holliday, EG, Terwindt, GM, Sturm, J, Bis, JC, Hopewell, JC, Ferrari, MD, Rannikmae, K, Wessman, M, Kallela, M, Kubisch, C, Fornage, M, Meschia, JF, Lehtimäki, T, Sudlow, C, Clarke, R, Chasman, DI, Mitchell, BD, Maguire, J, Kaprio, J, Farrall, M, Raitakari, OT, Kurth, T, Ikram, AM, Reiner, AP, Longstreth, WT, Rothwell, PM, Strachan, DP, Sharma, P, Seshadri, S, Quaye, L, Cherkas, L, Schürks, M, Rosand, J, Ligthart, L, Boncoraglio, GB, Smith, GDavey, van Duijn, CM, Stefansson, K, Worrall, BB, Nyholt, DR, Markus, HS, van den Maagdenberg, AMJM, Cotsapas, C, Zwart, JA, Palotie, A, Dichgans, M |
| Corporate/Institutional Authors | International Headache Genetics Consortium, METASTROKE Collaboration of the International Stroke Genetics Consortium |
| Journal | Neurology |
| Volume | 84 |
| Issue | 21 |
| Pagination | 2132-45 |
| Date Published | 2015 May 26 |
| ISSN | 1526-632X |
| Keywords | Brain Ischemia, Genome-Wide Association Study, Humans, Migraine with Aura, Migraine without Aura, Stroke |
| Abstract | <p><b>OBJECTIVE: </b>To quantify genetic overlap between migraine and ischemic stroke (IS) with respect to common genetic variation.</p><p><b>METHODS: </b>We applied 4 different approaches to large-scale meta-analyses of genome-wide data on migraine (23,285 cases and 95,425 controls) and IS (12,389 cases and 62,004 controls). First, we queried known genome-wide significant loci for both disorders, looking for potential overlap of signals. We then analyzed the overall shared genetic load using polygenic scores and estimated the genetic correlation between disease subtypes using data derived from these models. We further interrogated genomic regions of shared risk using analysis of covariance patterns between the 2 phenotypes using cross-phenotype spatial mapping.</p><p><b>RESULTS: </b>We found substantial genetic overlap between migraine and IS using all 4 approaches. Migraine without aura (MO) showed much stronger overlap with IS and its subtypes than migraine with aura (MA). The strongest overlap existed between MO and large artery stroke (LAS; p = 6.4 × 10(-28) for the LAS polygenic score in MO) and between MO and cardioembolic stroke (CE; p = 2.7 × 10(-20) for the CE score in MO).</p><p><b>CONCLUSIONS: </b>Our findings indicate shared genetic susceptibility to migraine and IS, with a particularly strong overlap between MO and both LAS and CE pointing towards shared mechanisms. Our observations on MA are consistent with a limited role of common genetic variants in this subtype.</p> |
| DOI | 10.1212/WNL.0000000000001606 |
| Alternate Journal | Neurology |
| PubMed ID | 25934857 |
| PubMed Central ID | PMC4451048 |
| Grant List | 0600331 / / Medical Research Council / United Kingdom 068545/Z/02 / / Wellcome Trust / United Kingdom 076113/B/04/Z / / Wellcome Trust / United Kingdom 079895 / / Wellcome Trust / United Kingdom 085475/B/08/Z / / Wellcome Trust / United Kingdom 085475/Z/08/z / / Wellcome Trust / United Kingdom 090532/Z/09/Z / / Wellcome Trust / United Kingdom 092731 / / Wellcome Trust / United Kingdom 095626 / / Wellcome Trust / United Kingdom 1RL1MH083268‐01 / MH / NIMH NIH HHS / United States 5R01HL087679‐02 / HL / NHLBI NIH HHS / United States 5R01MH63706:02 / MH / NIMH NIH HHS / United States AA07535 / AA / NIAAA NIH HHS / United States AA07728 / AA / NIAAA NIH HHS / United States AA11998 / AA / NIAAA NIH HHS / United States AA13320 / AA / NIAAA NIH HHS / United States AA13321 / AA / NIAAA NIH HHS / United States AA14041 / AA / NIAAA NIH HHS / United States AA15416 / AA / NIAAA NIH HHS / United States AA17688 / AA / NIAAA NIH HHS / United States AA‐00145 / AA / NIAAA NIH HHS / United States AA‐09203 / AA / NIAAA NIH HHS / United States AA‐12502 / AA / NIAAA NIH HHS / United States AG-023629 / AG / NIA NIH HHS / United States AG-027058 / AG / NIA NIH HHS / United States AG-15928 / AG / NIA NIH HHS / United States AG-20098 / AG / NIA NIH HHS / United States AG033193 / AG / NIA NIH HHS / United States CA‐47988 / CA / NCI NIH HHS / United States DA012854 / DA / NIDA NIH HHS / United States DA019951 / DA / NIDA NIH HHS / United States G0000934 / / Medical Research Council / United Kingdom G0500539 / / Medical Research Council / United Kingdom G0600331 / / Medical Research Council / United Kingdom G0600705 / / Medical Research Council / United Kingdom GR069224 / / Wellcome Trust / United Kingdom HL-093029 / HL / NHLBI NIH HHS / United States HL080295 / HL / NHLBI NIH HHS / United States HL087652 / HL / NHLBI NIH HHS / United States HL105756 / HL / NHLBI NIH HHS / United States HL93029 / HL / NHLBI NIH HHS / United States HL‐043851 / HL / NHLBI NIH HHS / United States HL‐080467 / HL / NHLBI NIH HHS / United States HL‐099355 / HL / NHLBI NIH HHS / United States K02AA018755 / AA / NIAAA NIH HHS / United States MH081802 / MH / NIMH NIH HHS / United States NS17950 / NS / NINDS NIH HHS / United States NS‐061836 / NS / NINDS NIH HHS / United States OSRP2/1006 / / The Dunhill Medical Trust / United Kingdom P30 DK072488 / DK / NIDDK NIH HHS / United States P30DK072488 / DK / NIDDK NIH HHS / United States R01 AG033193 / AG / NIA NIH HHS / United States R01 HL073410 / HL / NHLBI NIH HHS / United States R01 HL085251 / HL / NHLBI NIH HHS / United States R01 HL087676 / HL / NHLBI NIH HHS / United States R01 NS-39987 / NS / NINDS NIH HHS / United States R01 NS-42733 / NS / NINDS NIH HHS / United States R01 NS45012 / NS / NINDS NIH HHS / United States R01-HL087641 / HL / NHLBI NIH HHS / United States R01-HL093029 / HL / NHLBI NIH HHS / United States R01D0042157‐01A / / PHS HHS / United States R01HL086694 / HL / NHLBI NIH HHS / United States R01HL087641 / HL / NHLBI NIH HHS / United States R01HL59367 / HL / NHLBI NIH HHS / United States U01 DK062418 / DK / NIDDK NIH HHS / United States U01 HG 004446 / HG / NHGRI NIH HHS / United States U01 HL096917 / HL / NHLBI NIH HHS / United States U01 NS069208 / NS / NINDS NIH HHS / United States U01HG004436 / HG / NHGRI NIH HHS / United States U01NS069208-01 / NS / NINDS NIH HHS / United States U54 RR020278 / RR / NCRR NIH HHS / United States UL1RR025005 / RR / NCRR NIH HHS / United States UL1RR033176 / RR / NCRR NIH HHS / United States UL1TR000124 / TR / NCATS NIH HHS / United States UM1 CA182913 / CA / NCI NIH HHS / United States WT084724MA / / Wellcome Trust / United Kingdom WT089062 / / Wellcome Trust / United Kingdom WT089549 / / Wellcome Trust / United Kingdom Z01 AG-000015-50 / AG / NIA NIH HHS / United States Z01 AG-000954-06 / AG / NIA NIH HHS / United States |