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Gene-based pleiotropy across migraine with aura and migraine without aura patient groups

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Gene-based pleiotropy across migraine with aura and migraine without aura patient groups. / Zhao, Huiying; Eising, Else; de Vries, Boukje; Vijfhuizen, Lisanne S; Anttila, Verneri; Winsvold, Bendik S; Kurth, Tobias; Stefansson, Hreinn; Kallela, Mikko; Malik, Rainer; Stam, Anine H; Ikram, M Arfan; Ligthart, Lannie; Freilinger, Tobias; Alexander, Michael; Müller-Myhsok, Bertram; Schreiber, Stefan; Meitinger, Thomas; Aromas, Arpo; Eriksson, Johan G; Boomsma, Dorret I; van Duijn, Cornelia M; Zwart, John-Anker; Quaye, Lydia; Kubisch, Christian; Dichgans, Martin; Wessman, Maija; Stefansson, Kari; Chasman, Daniel I; Palotie, Aarno; Martin, Nicholas G; Montgomery, Grant W; Ferrari, Michel D; Terwindt, Gisela M; van den Maagdenberg, Arn M J M; Nyholt, Dale R; International Headache Genetics Consortium.

In: CEPHALALGIA, Vol. 36, No. 7, 01.06.2016, p. 648-57.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Zhao, H, Eising, E, de Vries, B, Vijfhuizen, LS, Anttila, V, Winsvold, BS, Kurth, T, Stefansson, H, Kallela, M, Malik, R, Stam, AH, Ikram, MA, Ligthart, L, Freilinger, T, Alexander, M, Müller-Myhsok, B, Schreiber, S, Meitinger, T, Aromas, A, Eriksson, JG, Boomsma, DI, van Duijn, CM, Zwart, J-A, Quaye, L, Kubisch, C, Dichgans, M, Wessman, M, Stefansson, K, Chasman, DI, Palotie, A, Martin, NG, Montgomery, GW, Ferrari, MD, Terwindt, GM, van den Maagdenberg, AMJM, Nyholt, DR & International Headache Genetics Consortium 2016, 'Gene-based pleiotropy across migraine with aura and migraine without aura patient groups', CEPHALALGIA, vol. 36, no. 7, pp. 648-57. https://doi.org/10.1177/0333102415591497

APA

Zhao, H., Eising, E., de Vries, B., Vijfhuizen, L. S., Anttila, V., Winsvold, B. S., Kurth, T., Stefansson, H., Kallela, M., Malik, R., Stam, A. H., Ikram, M. A., Ligthart, L., Freilinger, T., Alexander, M., Müller-Myhsok, B., Schreiber, S., Meitinger, T., Aromas, A., ... International Headache Genetics Consortium (2016). Gene-based pleiotropy across migraine with aura and migraine without aura patient groups. CEPHALALGIA, 36(7), 648-57. https://doi.org/10.1177/0333102415591497

Vancouver

Zhao H, Eising E, de Vries B, Vijfhuizen LS, Anttila V, Winsvold BS et al. Gene-based pleiotropy across migraine with aura and migraine without aura patient groups. CEPHALALGIA. 2016 Jun 1;36(7):648-57. https://doi.org/10.1177/0333102415591497

Bibtex

@article{f5799deba69c49ccbd65895443352e9e,
title = "Gene-based pleiotropy across migraine with aura and migraine without aura patient groups",
abstract = "INTRODUCTION: H.Z. and E.E. contributed equally to this work. A.M.J.M.v.d.M. and D.R.N. jointly directed this work.It is unclear whether patients diagnosed according to International Classification of Headache Disorders criteria for migraine with aura (MA) and migraine without aura (MO) experience distinct disorders or whether their migraine subtypes are genetically related.AIM: Using a novel gene-based (statistical) approach, we aimed to identify individual genes and pathways associated both with MA and MO.METHODS: Gene-based tests were performed using genome-wide association summary statistic results from the most recent International Headache Genetics Consortium study comparing 4505 MA cases with 34,813 controls and 4038 MO cases with 40,294 controls. After accounting for non-independence of gene-based test results, we examined the significance of the proportion of shared genes associated with MA and MO.RESULTS: We found a significant overlap in genes associated with MA and MO. Of the total 1514 genes with a nominally significant gene-based p value (pgene-based ≤ 0.05) in the MA subgroup, 107 also produced pgene-based ≤ 0.05 in the MO subgroup. The proportion of overlapping genes is almost double the empirically derived null expectation, producing significant evidence of gene-based overlap (pleiotropy) (pbinomial-test = 1.5 × 10(-4)). Combining results across MA and MO, six genes produced genome-wide significant gene-based p values. Four of these genes (TRPM8, UFL1, FHL5 and LRP1) were located in close proximity to previously reported genome-wide significant SNPs for migraine, while two genes, TARBP2 and NPFF separated by just 259 bp on chromosome 12q13.13, represent a novel risk locus. The genes overlapping in both migraine types were enriched for functions related to inflammation, the cardiovascular system and connective tissue.CONCLUSIONS: Our results provide novel insight into the likely genes and biological mechanisms that underlie both MA and MO, and when combined with previous data, highlight the neuropeptide FF-amide peptide encoding gene (NPFF) as a novel candidate risk gene for both types of migraine.",
author = "Huiying Zhao and Else Eising and {de Vries}, Boukje and Vijfhuizen, {Lisanne S} and Verneri Anttila and Winsvold, {Bendik S} and Tobias Kurth and Hreinn Stefansson and Mikko Kallela and Rainer Malik and Stam, {Anine H} and Ikram, {M Arfan} and Lannie Ligthart and Tobias Freilinger and Michael Alexander and Bertram M{\"u}ller-Myhsok and Stefan Schreiber and Thomas Meitinger and Arpo Aromas and Eriksson, {Johan G} and Boomsma, {Dorret I} and {van Duijn}, {Cornelia M} and John-Anker Zwart and Lydia Quaye and Christian Kubisch and Martin Dichgans and Maija Wessman and Kari Stefansson and Chasman, {Daniel I} and Aarno Palotie and Martin, {Nicholas G} and Montgomery, {Grant W} and Ferrari, {Michel D} and Terwindt, {Gisela M} and {van den Maagdenberg}, {Arn M J M} and Nyholt, {Dale R} and {International Headache Genetics Consortium}",
note = "{\textcopyright} International Headache Society 2015.",
year = "2016",
month = jun,
day = "1",
doi = "10.1177/0333102415591497",
language = "English",
volume = "36",
pages = "648--57",
journal = "CEPHALALGIA",
issn = "0333-1024",
publisher = "SAGE Publications",
number = "7",

}

RIS

TY - JOUR

T1 - Gene-based pleiotropy across migraine with aura and migraine without aura patient groups

AU - Zhao, Huiying

AU - Eising, Else

AU - de Vries, Boukje

AU - Vijfhuizen, Lisanne S

AU - Anttila, Verneri

AU - Winsvold, Bendik S

AU - Kurth, Tobias

AU - Stefansson, Hreinn

AU - Kallela, Mikko

AU - Malik, Rainer

AU - Stam, Anine H

AU - Ikram, M Arfan

AU - Ligthart, Lannie

AU - Freilinger, Tobias

AU - Alexander, Michael

AU - Müller-Myhsok, Bertram

AU - Schreiber, Stefan

AU - Meitinger, Thomas

AU - Aromas, Arpo

AU - Eriksson, Johan G

AU - Boomsma, Dorret I

AU - van Duijn, Cornelia M

AU - Zwart, John-Anker

AU - Quaye, Lydia

AU - Kubisch, Christian

AU - Dichgans, Martin

AU - Wessman, Maija

AU - Stefansson, Kari

AU - Chasman, Daniel I

AU - Palotie, Aarno

AU - Martin, Nicholas G

AU - Montgomery, Grant W

AU - Ferrari, Michel D

AU - Terwindt, Gisela M

AU - van den Maagdenberg, Arn M J M

AU - Nyholt, Dale R

AU - International Headache Genetics Consortium

N1 - © International Headache Society 2015.

PY - 2016/6/1

Y1 - 2016/6/1

N2 - INTRODUCTION: H.Z. and E.E. contributed equally to this work. A.M.J.M.v.d.M. and D.R.N. jointly directed this work.It is unclear whether patients diagnosed according to International Classification of Headache Disorders criteria for migraine with aura (MA) and migraine without aura (MO) experience distinct disorders or whether their migraine subtypes are genetically related.AIM: Using a novel gene-based (statistical) approach, we aimed to identify individual genes and pathways associated both with MA and MO.METHODS: Gene-based tests were performed using genome-wide association summary statistic results from the most recent International Headache Genetics Consortium study comparing 4505 MA cases with 34,813 controls and 4038 MO cases with 40,294 controls. After accounting for non-independence of gene-based test results, we examined the significance of the proportion of shared genes associated with MA and MO.RESULTS: We found a significant overlap in genes associated with MA and MO. Of the total 1514 genes with a nominally significant gene-based p value (pgene-based ≤ 0.05) in the MA subgroup, 107 also produced pgene-based ≤ 0.05 in the MO subgroup. The proportion of overlapping genes is almost double the empirically derived null expectation, producing significant evidence of gene-based overlap (pleiotropy) (pbinomial-test = 1.5 × 10(-4)). Combining results across MA and MO, six genes produced genome-wide significant gene-based p values. Four of these genes (TRPM8, UFL1, FHL5 and LRP1) were located in close proximity to previously reported genome-wide significant SNPs for migraine, while two genes, TARBP2 and NPFF separated by just 259 bp on chromosome 12q13.13, represent a novel risk locus. The genes overlapping in both migraine types were enriched for functions related to inflammation, the cardiovascular system and connective tissue.CONCLUSIONS: Our results provide novel insight into the likely genes and biological mechanisms that underlie both MA and MO, and when combined with previous data, highlight the neuropeptide FF-amide peptide encoding gene (NPFF) as a novel candidate risk gene for both types of migraine.

AB - INTRODUCTION: H.Z. and E.E. contributed equally to this work. A.M.J.M.v.d.M. and D.R.N. jointly directed this work.It is unclear whether patients diagnosed according to International Classification of Headache Disorders criteria for migraine with aura (MA) and migraine without aura (MO) experience distinct disorders or whether their migraine subtypes are genetically related.AIM: Using a novel gene-based (statistical) approach, we aimed to identify individual genes and pathways associated both with MA and MO.METHODS: Gene-based tests were performed using genome-wide association summary statistic results from the most recent International Headache Genetics Consortium study comparing 4505 MA cases with 34,813 controls and 4038 MO cases with 40,294 controls. After accounting for non-independence of gene-based test results, we examined the significance of the proportion of shared genes associated with MA and MO.RESULTS: We found a significant overlap in genes associated with MA and MO. Of the total 1514 genes with a nominally significant gene-based p value (pgene-based ≤ 0.05) in the MA subgroup, 107 also produced pgene-based ≤ 0.05 in the MO subgroup. The proportion of overlapping genes is almost double the empirically derived null expectation, producing significant evidence of gene-based overlap (pleiotropy) (pbinomial-test = 1.5 × 10(-4)). Combining results across MA and MO, six genes produced genome-wide significant gene-based p values. Four of these genes (TRPM8, UFL1, FHL5 and LRP1) were located in close proximity to previously reported genome-wide significant SNPs for migraine, while two genes, TARBP2 and NPFF separated by just 259 bp on chromosome 12q13.13, represent a novel risk locus. The genes overlapping in both migraine types were enriched for functions related to inflammation, the cardiovascular system and connective tissue.CONCLUSIONS: Our results provide novel insight into the likely genes and biological mechanisms that underlie both MA and MO, and when combined with previous data, highlight the neuropeptide FF-amide peptide encoding gene (NPFF) as a novel candidate risk gene for both types of migraine.

U2 - 10.1177/0333102415591497

DO - 10.1177/0333102415591497

M3 - SCORING: Journal article

C2 - 26660531

VL - 36

SP - 648

EP - 657

JO - CEPHALALGIA

JF - CEPHALALGIA

SN - 0333-1024

IS - 7

ER -