Editing Migraine (section)

===Genetics===
{{Main|Genetics of migraine}}

[[Twin study|Studies of twins]] indicate a 34–51% genetic influence on the likelihood of developing migraine.<ref name="Lulli2007" /> This genetic relationship is stronger for migraine with aura than for migraine without aura.<ref name="Olesen_2006" /> It is clear from family and [[Population studies|populations studies]] that migraine is a [[disease|complex disorder]], where numerous [[single-nucleotide polymorphism|genetic risk variants]] exist, and where each variant increases the risk of migraine marginally.<ref>{{cite journal | vauthors = Gormley P, Kurki MI, Hiekkala ME, Veerapen K, Häppölä P, Mitchell AA, Lal D, Palta P, Surakka I, Kaunisto MA, Hämäläinen E, Vepsäläinen S, Havanka H, Harno H, Ilmavirta M, Nissilä M, Säkö E, Sumelahti ML, Liukkonen J, Sillanpää M, Metsähonkala L, Koskinen S, Lehtimäki T, Raitakari O, Männikkö M, Ran C, Belin AC, Jousilahti P, Anttila V, Salomaa V, Artto V, Färkkilä M, Runz H, Daly MJ, Neale BM, Ripatti S, Kallela M, Wessman M, Palotie A | title = Common Variant Burden Contributes to the Familial Aggregation of Migraine in 1,589 Families | journal = Neuron | volume = 98 | issue = 4 | pages = 743–753.e4 | date = May 2018 | pmid = 29731251 | pmc = 5967411 | doi = 10.1016/j.neuron.2018.04.014 }}</ref><ref>{{cite journal | vauthors = Harder AV, Terwindt GM, Nyholt DR, van den Maagdenberg AM | title = Migraine genetics: Status and road forward | journal = Cephalalgia | volume = 43 | issue = 2 | pages = 3331024221145962 | date = February 2023 | pmid = 36759319 | doi = 10.1177/03331024221145962 | doi-access = free }}</ref> It is also known that having several of these risk variants increases the risk by a small to moderate amount.<ref name="Schurk2012" />

[[Single gene disorder]]s that result in migraine are rare.<ref name=Schurk2012>{{cite journal | vauthors = Schürks M | title = Genetics of migraine in the age of genome-wide association studies | journal = The Journal of Headache and Pain | volume = 13 | issue = 1 | pages = 1–9 | date = January 2012 | pmid = 22072275 | pmc = 3253157 | doi = 10.1007/s10194-011-0399-0 }}</ref> One of these is known as [[familial hemiplegic migraine]], a type of migraine with aura, which is inherited in an [[autosomal dominant]] fashion.<ref>{{cite journal | vauthors = de Vries B, Frants RR, Ferrari MD, van den Maagdenberg AM | title = Molecular genetics of migraine | journal = Human Genetics | volume = 126 | issue = 1 | pages = 115–32 | date = July 2009 | pmid = 19455354 | doi = 10.1007/s00439-009-0684-z | s2cid = 20119237 }}</ref><ref>{{cite journal | vauthors = Montagna P | title = Migraine genetics | journal = Expert Review of Neurotherapeutics | volume = 8 | issue = 9 | pages = 1321–30 | date = September 2008 | pmid = 18759544 | doi = 10.1586/14737175.8.9.1321 | s2cid = 207195127 }}</ref> Four genes have been shown to be involved in familial hemiplegic migraine.<ref name=Ducros2013>{{cite journal | vauthors = Ducros A | title = [Genetics of migraine] | journal = Revue Neurologique | volume = 169 | issue = 5 | pages = 360–71 | date = May 2013 | pmid = 23618705 | doi = 10.1016/j.neurol.2012.11.010 }}</ref> Three of these genes are involved in [[ion transport]].<ref name=Ducros2013/> The fourth is the [[axon]]al protein [[PRRT2]], associated with the [[exocytosis]] complex.<ref name=Ducros2013/> Another genetic disorder associated with migraine is [[CADASIL syndrome]] or cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.<ref name=Amin2009/> One meta-analysis found a protective effect from [[angiotensin converting enzyme]] polymorphisms on migraine.<ref>{{cite journal | vauthors = Wan D, Wang C, Zhang X, Tang W, Chen M, Dong Z, Yu S | title = Association between angiotensin-converting enzyme insertion/deletion polymorphism and migraine: a meta-analysis | journal = The International Journal of Neuroscience | volume = 126 | issue = 5 | pages = 393–9 | date = 1 January 2016 | pmid = 26000817 | doi = 10.3109/00207454.2015.1025395 | s2cid = 34902092 }}</ref> The ''[[TRPM8]]'' gene, which codes for a [[Ion channel|cation channel]], has been linked to migraine.<ref>{{cite journal | vauthors = Dussor G, Cao YQ | title = TRPM8 and Migraine | journal = Headache | volume = 56 | issue = 9 | pages = 1406–1417 | date = October 2016 | pmid = 27634619 | pmc = 5335856 | doi = 10.1111/head.12948 }}</ref>

The common forms migraine are [[Polygenic trait|polygenetic]], where common variants of numerous genes contributes to the predisposition for migraine.  These genes can be placed in three categories increasing the risk of migraine in general, specifically migraine with aura, or migraine without aura.<ref>{{cite journal | vauthors = Bjornsdottir G, Chalmer MA, Stefansdottir L, Skuladottir AT, Einarsson G, Andresdottir M, Beyter D, Ferkingstad E, Gretarsdottir S, Halldorsson BV, Halldorsson GH, Helgadottir A, Helgason H, Hjorleifsson Eldjarn G, Jonasdottir A, Jonasdottir A, Jonsdottir I, Knowlton KU, Nadauld LD, Lund SH, Magnusson OT, Melsted P, Moore KH, Oddsson A, Olason PI, Sigurdsson A, Stefansson OA, Saemundsdottir J, Sveinbjornsson G, Tragante V, Unnsteinsdottir U, Walters GB, Zink F, Rødevand L, Andreassen OA, Igland J, Lie RT, Haavik J, Banasik K, Brunak S, Didriksen M, T Bruun M, Erikstrup C, Kogelman LJ, Nielsen KR, Sørensen E, Pedersen OB, Ullum H, Masson G, Thorsteinsdottir U, Olesen J, Ludvigsson P, Thorarensen O, Bjornsdottir A, Sigurdardottir GR, Sveinsson OA, Ostrowski SR, Holm H, Gudbjartsson DF, Thorleifsson G, Sulem P, Stefansson H, Thorgeirsson TE, Hansen TF, Stefansson K | title = Rare variants with large effects provide functional insights into the pathology of migraine subtypes, with and without aura | journal = Nature Genetics | volume = 55 | issue = 11 | pages = 1843–1853 | date = November 2023 | pmid = 37884687 | pmc = 10632135 | doi = 10.1038/s41588-023-01538-0 }}</ref><ref>{{cite journal | vauthors = Hautakangas H, Winsvold BS, Ruotsalainen SE, Bjornsdottir G, Harder AV, Kogelman LJ, Thomas LF, Noordam R, Benner C, Gormley P, Artto V, Banasik K, Bjornsdottir A, Boomsma DI, Brumpton BM, Burgdorf KS, Buring JE, Chalmer MA, de Boer I, Dichgans M, Erikstrup C, Färkkilä M, Garbrielsen ME, Ghanbari M, Hagen K, Häppölä P, Hottenga JJ, Hrafnsdottir MG, Hveem K, Johnsen MB, Kähönen M, Kristoffersen ES, Kurth T, Lehtimäki T, Lighart L, Magnusson SH, Malik R, Pedersen OB, Pelzer N, Penninx BW, Ran C, Ridker PM, Rosendaal FR, Sigurdardottir GR, Skogholt AH, Sveinsson OA, Thorgeirsson TE, Ullum H, Vijfhuizen LS, Widén E, van Dijk KW, Aromaa A, Belin AC, Freilinger T, Ikram MA, Järvelin MR, Raitakari OT, Terwindt GM, Kallela M, Wessman M, Olesen J, Chasman DI, Nyholt DR, Stefánsson H, Stefansson K, van den Maagdenberg AM, Hansen TF, Ripatti S, Zwart JA, Palotie A, Pirinen M | title = Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles | journal = Nature Genetics | volume = 54 | issue = 2 | pages = 152–160 | date = February 2022 | pmid = 35115687 | doi = 10.1038/s41588-021-00990-0 | pmc = 8837554 }}</ref> Three of these genes, ''[[CALCA]]'', ''[[CALCB]]'', and ''[[HTR1F]]'' are already target for migraine specific treatments. Five genes are specific risk to migraine with aura, ''[[PALM|PALMD]]'', ''[[ABO blood group system|ABO]]'', ''[[LRRK2]], [[CACNA1A]]'' and ''PRRT2'', and 13 genes are specific to migraine without aura. Using the accumulated genetic risk of the common variations, into a so-called [[Polygenic score|polygenetic risk]], it is possible to assess e.g. the treatment response to triptans.<ref>{{Cite journal | vauthors = Mikol DD, Picard H, Klatt J, Wang A, Peng C, Stefansson K |date=2020-04-14 |title=Migraine Polygenic Risk Score Is Associated with Severity of Migraine – Analysis of Genotypic Data from Four Placebo-controlled Trials of Erenumab (1214) |url=https://www.neurology.org/doi/10.1212/WNL.94.15_supplement.1214 |journal=Neurology |volume=94 |issue=15_supplement |doi=10.1212/WNL.94.15_supplement.1214 |issn=0028-3878}}</ref><ref>{{cite journal | vauthors = Kogelman LJ, Esserlind AL, Francke Christensen A, Awasthi S, Ripke S, Ingason A, Davidsson OB, Erikstrup C, Hjalgrim H, Ullum H, Olesen J, Folkmann Hansen T | title = Migraine polygenic risk score associates with efficacy of migraine-specific drugs | journal = Neurology. Genetics | volume = 5 | issue = 6 | pages = e364 | date = December 2019 | pmid = 31872049 | pmc = 6878840 | doi = 10.1212/NXG.0000000000000364 }}</ref>