Association and genetic overlap between clinical chemistry tests and migraine

Hamzeh M. Tanha; Nicholas G. Martin; John B. Whitfield; Dale R. Nyholt; Padhraig Gormley; Verneri Anttila; Bendik S. Winsvold; Priit Palta; Tonu Esko; Tune H. Pers; Kai How Farh; Ester Cuenca-Leon; Mikko Muona; Nicholas A. Furlotte; Tobias Kurth; Andres Ingason; George McMahon; Lannie Ligthart; Gisela M. Terwindt; Mikko Kallela; Tobias M. Freilinger; Caroline Ran; Scott G. Gordon; Anine H. Stam; Stacy Steinberg; Guntram Borck; Markku Koiranen; Lydia Quaye; Hieab H.H. Adams; Terho Lehtim€aki; Antti Pekka Sarin; Juho Wedenoja; David A. Hinds; Julie E. Buring; Markus Schurks; Paul M. Ridker; Maria Gudlaug Hrafnsdottir; Hreinn Stefansson; Susan M. Ring; Jouke Jan Hottenga; Brenda WJH Penninx; Markus F€arkkil€a; Ville Artto; Mari Kaunisto; Salli Veps€al€ainen; Rainer Malik; Andrew C. Heath; Pamela AF Madden; Grant W. Montgomery; Mitja I. Kurki; Mart Kals; Reedik M€agi; Kalle P€arn; Eija H€am€al€ainen; Hailiang Huang; Andrea E. Byrnes; Lude Franke; Jie Huang; Evie Stergiakouli; Phil H. Lee; Cynthia Sandor; Caleb Webber; Zameel Cader; Bertram Muller-Myhsok; Stefan Schreiber; Thomas Meitinger; Johan G. Eriksson; Veikko Salomaa; Kauko Heikkil€a; Elizabeth Loehrer; Andre G. Uitterlinden; Albert Hofman; Cornelia M. van Duijn; Lynn Cherkas; Linda M. Pedersen; Audun Stubhaug; Christopher S. Nielsen; Minna M€annikk€o; Evelin Mihailov; Lili Milani; Hartmut G€obel; Ann Louise Esserlind; Anne Francke Christensen; Thomas Folkmann Hansen; Thomas Werge; Jaakko Kaprio; Arpo J. Aromaa; Olli Raitakari; M. Arfan Ikram; Tim Spector; Marjo Riitta J€arvelin; Andres Metspalu; Christian Kubisch; David P. Strachan; Michel D. Ferrari; Andrea C. Belin; Martin Dichgans; Maija Wessman; Arn M.J.M. van den Maagdenberg; John Anker Zwart; Dorret I. Boomsma; George Davey Smith; Kari Stefansson; Nicholas Eriksson; Mark J. Daly; Benjamin M. Neale; Jes Olesen; Daniel I. Chasman; Aarno Palotie

doi:10.1177/03331024211018131

Association and genetic overlap between clinical chemistry tests and migraine

Hamzeh M. Tanha, Nicholas G. Martin, John B. Whitfield, Dale R. Nyholt, Padhraig Gormley, Verneri Anttila, Bendik S. Winsvold, Priit Palta, Tonu Esko, Tune H. Pers, Kai How Farh, Ester Cuenca-Leon, Mikko Muona, Nicholas A. Furlotte, Tobias Kurth, Andres Ingason, George McMahon, Lannie Ligthart, Gisela M. Terwindt, Mikko KallelaTobias M. Freilinger, Caroline Ran, Scott G. Gordon, Anine H. Stam, Stacy Steinberg, Guntram Borck, Markku Koiranen, Lydia Quaye, Hieab H.H. Adams, Terho Lehtim€aki, Antti Pekka Sarin, Juho Wedenoja, David A. Hinds, Julie E. Buring, Markus Schurks, Paul M. Ridker, Maria Gudlaug Hrafnsdottir, Hreinn Stefansson, Susan M. Ring, Jouke Jan Hottenga, Brenda WJH Penninx, Markus F€arkkil€a, Ville Artto, Mari Kaunisto, Salli Veps€al€ainen, Rainer Malik, Andrew C. Heath, Pamela AF Madden, Grant W. Montgomery, Mitja I. Kurki, Mart Kals, Reedik M€agi, Kalle P€arn, Eija H€am€al€ainen, Hailiang Huang, Andrea E. Byrnes, Lude Franke, Jie Huang, Evie Stergiakouli, Phil H. Lee, Cynthia Sandor, Caleb Webber, Zameel Cader, Bertram Muller-Myhsok, Stefan Schreiber, Thomas Meitinger, Johan G. Eriksson, Veikko Salomaa, Kauko Heikkil€a, Elizabeth Loehrer, Andre G. Uitterlinden, Albert Hofman, Cornelia M. van Duijn, Lynn Cherkas, Linda M. Pedersen, Audun Stubhaug, Christopher S. Nielsen, Minna M€annikk€o, Evelin Mihailov, Lili Milani, Hartmut G€obel, Ann Louise Esserlind, Anne Francke Christensen, Thomas Folkmann Hansen, Thomas Werge, Jaakko Kaprio, Arpo J. Aromaa, Olli Raitakari, M. Arfan Ikram, Tim Spector, Marjo Riitta J€arvelin, Andres Metspalu, Christian Kubisch, David P. Strachan, Michel D. Ferrari, Andrea C. Belin, Martin Dichgans, Maija Wessman, Arn M.J.M. van den Maagdenberg, John Anker Zwart, Dorret I. Boomsma, George Davey Smith, Kari Stefansson, Nicholas Eriksson, Mark J. Daly, Benjamin M. Neale, Jes Olesen, Daniel I. Chasman, Aarno Palotie

Research output: Contribution to journal › Article › peer-review

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Abstract

Introduction: In this paper, we studied several serum clinical chemistry tests of cardiovascular disease (CVD), iron deficiency anemia, liver and kidney disorders in migraine. Methods: We first explored the association of 22 clinical chemistry tests with migraine risk in 697 migraine patients and 2722 controls. To validate and interpret association findings, cross-trait genetic analyses were conducted utilising genome-wide association study (GWAS) data comprising 23,986 to 452,264 individuals. Results: Significant associations with migraine risk were identified for biomarkers of CVD risk, iron deficiency and liver dysfunction (odds ratios = 0.86–1.21; 1 × 10⁻⁴ < p < 3 × 10⁻²). Results from cross-trait genetic analyses corroborate the significant biomarker associations and indicate their relationship with migraine is more consistent with biological pleiotropy than causality. For example, association and genetic overlap between a lower level of HDL-C and increased migraine risk are due to shared biology rather than a causal relationship. Furthermore, additional genetic analyses revealed shared genetics among migraine, the clinical chemistry tests, and heart problems and iron deficiency anemia, but not liver disease. Conclusions: These findings highlight common biological mechanisms underlying migraine, heart problems and iron deficiency anemia and provide support for their investigation in the development of novel therapeutic and dietary interventions.

Original language	English
Pages (from-to)	1208-1221
Number of pages	14
Journal	Cephalalgia
Volume	41
Issue number	11-12
DOIs	https://doi.org/10.1177/03331024211018131
State	Published - Oct 2021

Keywords

Biochemistry tests
Mendelian randomisation
SNP-based genetic overlap
gene-based genetic overlap
genetic correlation

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10.1177/03331024211018131

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Tanha, H. M., Martin, N. G., Whitfield, J. B., Nyholt, D. R., Gormley, P., Anttila, V., Winsvold, B. S., Palta, P., Esko, T., Pers, T. H., Farh, K. H., Cuenca-Leon, E., Muona, M., Furlotte, N. A., Kurth, T., Ingason, A., McMahon, G., Ligthart, L., Terwindt, G. M., ... Palotie, A. (2021). Association and genetic overlap between clinical chemistry tests and migraine. Cephalalgia, 41(11-12), 1208-1221. https://doi.org/10.1177/03331024211018131

@article{9e30c639f7a54bbe917be41a826dfe78,

title = "Association and genetic overlap between clinical chemistry tests and migraine",

abstract = "Introduction: In this paper, we studied several serum clinical chemistry tests of cardiovascular disease (CVD), iron deficiency anemia, liver and kidney disorders in migraine. Methods: We first explored the association of 22 clinical chemistry tests with migraine risk in 697 migraine patients and 2722 controls. To validate and interpret association findings, cross-trait genetic analyses were conducted utilising genome-wide association study (GWAS) data comprising 23,986 to 452,264 individuals. Results: Significant associations with migraine risk were identified for biomarkers of CVD risk, iron deficiency and liver dysfunction (odds ratios = 0.86–1.21; 1 × 10−4 < p < 3 × 10−2). Results from cross-trait genetic analyses corroborate the significant biomarker associations and indicate their relationship with migraine is more consistent with biological pleiotropy than causality. For example, association and genetic overlap between a lower level of HDL-C and increased migraine risk are due to shared biology rather than a causal relationship. Furthermore, additional genetic analyses revealed shared genetics among migraine, the clinical chemistry tests, and heart problems and iron deficiency anemia, but not liver disease. Conclusions: These findings highlight common biological mechanisms underlying migraine, heart problems and iron deficiency anemia and provide support for their investigation in the development of novel therapeutic and dietary interventions.",

keywords = "Biochemistry tests, Mendelian randomisation, SNP-based genetic overlap, gene-based genetic overlap, genetic correlation",

author = "Tanha, {Hamzeh M.} and Martin, {Nicholas G.} and Whitfield, {John B.} and Nyholt, {Dale R.} and Padhraig Gormley and Verneri Anttila and Winsvold, {Bendik S.} and Priit Palta and Tonu Esko and Pers, {Tune H.} and Farh, {Kai How} and Ester Cuenca-Leon and Mikko Muona and Furlotte, {Nicholas A.} and Tobias Kurth and Andres Ingason and George McMahon and Lannie Ligthart and Terwindt, {Gisela M.} and Mikko Kallela and Freilinger, {Tobias M.} and Caroline Ran and Gordon, {Scott G.} and Stam, {Anine H.} and Stacy Steinberg and Guntram Borck and Markku Koiranen and Lydia Quaye and Adams, {Hieab H.H.} and Terho Lehtim€aki and Sarin, {Antti Pekka} and Juho Wedenoja and Hinds, {David A.} and Buring, {Julie E.} and Markus Schurks and Ridker, {Paul M.} and Hrafnsdottir, {Maria Gudlaug} and Hreinn Stefansson and Ring, {Susan M.} and Hottenga, {Jouke Jan} and Penninx, {Brenda WJH} and Markus F€arkkil€a and Ville Artto and Mari Kaunisto and Salli Veps€al€ainen and Rainer Malik and Heath, {Andrew C.} and Madden, {Pamela AF} and Montgomery, {Grant W.} and Kurki, {Mitja I.} and Mart Kals and Reedik M€agi and Kalle P€arn and Eija H€am€al€ainen and Hailiang Huang and Byrnes, {Andrea E.} and Lude Franke and Jie Huang and Evie Stergiakouli and Lee, {Phil H.} and Cynthia Sandor and Caleb Webber and Zameel Cader and Bertram Muller-Myhsok and Stefan Schreiber and Thomas Meitinger and Eriksson, {Johan G.} and Veikko Salomaa and Kauko Heikkil€a and Elizabeth Loehrer and Uitterlinden, {Andre G.} and Albert Hofman and {van Duijn}, {Cornelia M.} and Lynn Cherkas and Pedersen, {Linda M.} and Audun Stubhaug and Nielsen, {Christopher S.} and Minna M€annikk€o and Evelin Mihailov and Lili Milani and Hartmut G€obel and Esserlind, {Ann Louise} and Christensen, {Anne Francke} and Hansen, {Thomas Folkmann} and Thomas Werge and Jaakko Kaprio and Aromaa, {Arpo J.} and Olli Raitakari and Ikram, {M. Arfan} and Tim Spector and J€arvelin, {Marjo Riitta} and Andres Metspalu and Christian Kubisch and Strachan, {David P.} and Ferrari, {Michel D.} and Belin, {Andrea C.} and Martin Dichgans and Maija Wessman and {van den Maagdenberg}, {Arn M.J.M.} and Zwart, {John Anker} and Boomsma, {Dorret I.} and Smith, {George Davey} and Kari Stefansson and Nicholas Eriksson and Daly, {Mark J.} and Neale, {Benjamin M.} and Jes Olesen and Chasman, {Daniel I.} and Aarno Palotie",

note = "Publisher Copyright: {\textcopyright} International Headache Society 2021.",

year = "2021",

month = oct,

doi = "10.1177/03331024211018131",

language = "English",

volume = "41",

pages = "1208--1221",

journal = "Cephalalgia",

issn = "0333-1024",

number = "11-12",

}

Tanha, HM, Martin, NG, Whitfield, JB, Nyholt, DR, Gormley, P, Anttila, V, Winsvold, BS, Palta, P, Esko, T, Pers, TH, Farh, KH, Cuenca-Leon, E, Muona, M, Furlotte, NA, Kurth, T, Ingason, A, McMahon, G, Ligthart, L, Terwindt, GM, Kallela, M, Freilinger, TM, Ran, C, Gordon, SG, Stam, AH, Steinberg, S, Borck, G, Koiranen, M, Quaye, L, Adams, HHH, Lehtim€aki, T, Sarin, AP, Wedenoja, J, Hinds, DA, Buring, JE, Schurks, M, Ridker, PM, Hrafnsdottir, MG, Stefansson, H, Ring, SM, Hottenga, JJ, Penninx, BWJH, F€arkkil€a, M, Artto, V, Kaunisto, M, Veps€al€ainen, S, Malik, R, Heath, AC , Madden, PAF, Montgomery, GW, Kurki, MI, Kals, M, M€agi, R, P€arn, K, H€am€al€ainen, E, Huang, H, Byrnes, AE, Franke, L, Huang, J, Stergiakouli, E, Lee, PH, Sandor, C, Webber, C, Cader, Z, Muller-Myhsok, B, Schreiber, S, Meitinger, T, Eriksson, JG, Salomaa, V, Heikkil€a, K, Loehrer, E, Uitterlinden, AG, Hofman, A, van Duijn, CM, Cherkas, L, Pedersen, LM, Stubhaug, A, Nielsen, CS, M€annikk€o, M, Mihailov, E, Milani, L, G€obel, H, Esserlind, AL, Christensen, AF, Hansen, TF, Werge, T, Kaprio, J, Aromaa, AJ, Raitakari, O, Ikram, MA, Spector, T, J€arvelin, MR, Metspalu, A, Kubisch, C, Strachan, DP, Ferrari, MD, Belin, AC, Dichgans, M, Wessman, M, van den Maagdenberg, AMJM, Zwart, JA, Boomsma, DI, Smith, GD, Stefansson, K, Eriksson, N, Daly, MJ, Neale, BM, Olesen, J, Chasman, DI & Palotie, A 2021, 'Association and genetic overlap between clinical chemistry tests and migraine', Cephalalgia, vol. 41, no. 11-12, pp. 1208-1221. https://doi.org/10.1177/03331024211018131

TY - JOUR

T1 - Association and genetic overlap between clinical chemistry tests and migraine

AU - Tanha, Hamzeh M.

AU - Martin, Nicholas G.

AU - Whitfield, John B.

AU - Nyholt, Dale R.

AU - Gormley, Padhraig

AU - Anttila, Verneri

AU - Winsvold, Bendik S.

AU - Palta, Priit

AU - Esko, Tonu

AU - Pers, Tune H.

AU - Farh, Kai How

AU - Cuenca-Leon, Ester

AU - Muona, Mikko

AU - Furlotte, Nicholas A.

AU - Kurth, Tobias

AU - Ingason, Andres

AU - McMahon, George

AU - Ligthart, Lannie

AU - Terwindt, Gisela M.

AU - Kallela, Mikko

AU - Freilinger, Tobias M.

AU - Ran, Caroline

AU - Gordon, Scott G.

AU - Stam, Anine H.

AU - Steinberg, Stacy

AU - Borck, Guntram

AU - Koiranen, Markku

AU - Quaye, Lydia

AU - Adams, Hieab H.H.

AU - Lehtim€aki, Terho

AU - Sarin, Antti Pekka

AU - Wedenoja, Juho

AU - Hinds, David A.

AU - Buring, Julie E.

AU - Schurks, Markus

AU - Ridker, Paul M.

AU - Hrafnsdottir, Maria Gudlaug

AU - Stefansson, Hreinn

AU - Ring, Susan M.

AU - Hottenga, Jouke Jan

AU - Penninx, Brenda WJH

AU - F€arkkil€a, Markus

AU - Artto, Ville

AU - Kaunisto, Mari

AU - Veps€al€ainen, Salli

AU - Malik, Rainer

AU - Heath, Andrew C.

AU - Madden, Pamela AF

AU - Montgomery, Grant W.

AU - Kurki, Mitja I.

AU - Kals, Mart

AU - M€agi, Reedik

AU - P€arn, Kalle

AU - H€am€al€ainen, Eija

AU - Huang, Hailiang

AU - Byrnes, Andrea E.

AU - Franke, Lude

AU - Huang, Jie

AU - Stergiakouli, Evie

AU - Lee, Phil H.

AU - Sandor, Cynthia

AU - Webber, Caleb

AU - Cader, Zameel

AU - Muller-Myhsok, Bertram

AU - Schreiber, Stefan

AU - Meitinger, Thomas

AU - Eriksson, Johan G.

AU - Salomaa, Veikko

AU - Heikkil€a, Kauko

AU - Loehrer, Elizabeth

AU - Uitterlinden, Andre G.

AU - Hofman, Albert

AU - van Duijn, Cornelia M.

AU - Cherkas, Lynn

AU - Pedersen, Linda M.

AU - Stubhaug, Audun

AU - Nielsen, Christopher S.

AU - M€annikk€o, Minna

AU - Mihailov, Evelin

AU - Milani, Lili

AU - G€obel, Hartmut

AU - Esserlind, Ann Louise

AU - Christensen, Anne Francke

AU - Hansen, Thomas Folkmann

AU - Werge, Thomas

AU - Kaprio, Jaakko

AU - Aromaa, Arpo J.

AU - Raitakari, Olli

AU - Ikram, M. Arfan

AU - Spector, Tim

AU - J€arvelin, Marjo Riitta

AU - Metspalu, Andres

AU - Kubisch, Christian

AU - Strachan, David P.

AU - Ferrari, Michel D.

AU - Belin, Andrea C.

AU - Dichgans, Martin

AU - Wessman, Maija

AU - van den Maagdenberg, Arn M.J.M.

AU - Zwart, John Anker

AU - Boomsma, Dorret I.

AU - Smith, George Davey

AU - Stefansson, Kari

AU - Eriksson, Nicholas

AU - Daly, Mark J.

AU - Neale, Benjamin M.

AU - Olesen, Jes

AU - Chasman, Daniel I.

AU - Palotie, Aarno

PY - 2021/10

Y1 - 2021/10

N2 - Introduction: In this paper, we studied several serum clinical chemistry tests of cardiovascular disease (CVD), iron deficiency anemia, liver and kidney disorders in migraine. Methods: We first explored the association of 22 clinical chemistry tests with migraine risk in 697 migraine patients and 2722 controls. To validate and interpret association findings, cross-trait genetic analyses were conducted utilising genome-wide association study (GWAS) data comprising 23,986 to 452,264 individuals. Results: Significant associations with migraine risk were identified for biomarkers of CVD risk, iron deficiency and liver dysfunction (odds ratios = 0.86–1.21; 1 × 10−4 < p < 3 × 10−2). Results from cross-trait genetic analyses corroborate the significant biomarker associations and indicate their relationship with migraine is more consistent with biological pleiotropy than causality. For example, association and genetic overlap between a lower level of HDL-C and increased migraine risk are due to shared biology rather than a causal relationship. Furthermore, additional genetic analyses revealed shared genetics among migraine, the clinical chemistry tests, and heart problems and iron deficiency anemia, but not liver disease. Conclusions: These findings highlight common biological mechanisms underlying migraine, heart problems and iron deficiency anemia and provide support for their investigation in the development of novel therapeutic and dietary interventions.

AB - Introduction: In this paper, we studied several serum clinical chemistry tests of cardiovascular disease (CVD), iron deficiency anemia, liver and kidney disorders in migraine. Methods: We first explored the association of 22 clinical chemistry tests with migraine risk in 697 migraine patients and 2722 controls. To validate and interpret association findings, cross-trait genetic analyses were conducted utilising genome-wide association study (GWAS) data comprising 23,986 to 452,264 individuals. Results: Significant associations with migraine risk were identified for biomarkers of CVD risk, iron deficiency and liver dysfunction (odds ratios = 0.86–1.21; 1 × 10−4 < p < 3 × 10−2). Results from cross-trait genetic analyses corroborate the significant biomarker associations and indicate their relationship with migraine is more consistent with biological pleiotropy than causality. For example, association and genetic overlap between a lower level of HDL-C and increased migraine risk are due to shared biology rather than a causal relationship. Furthermore, additional genetic analyses revealed shared genetics among migraine, the clinical chemistry tests, and heart problems and iron deficiency anemia, but not liver disease. Conclusions: These findings highlight common biological mechanisms underlying migraine, heart problems and iron deficiency anemia and provide support for their investigation in the development of novel therapeutic and dietary interventions.

KW - Biochemistry tests

KW - Mendelian randomisation

KW - SNP-based genetic overlap

KW - gene-based genetic overlap

KW - genetic correlation

UR - http://www.scopus.com/inward/record.url?scp=85117387254&partnerID=8YFLogxK

U2 - 10.1177/03331024211018131

DO - 10.1177/03331024211018131

M3 - Article

C2 - 34130515

AN - SCOPUS:85117387254

SN - 0333-1024

VL - 41

SP - 1208

EP - 1221

JO - Cephalalgia

JF - Cephalalgia

IS - 11-12

ER -

Association and genetic overlap between clinical chemistry tests and migraine

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