Genetic risk score analysis indicates migraine with and without comorbid depression are genetically different disorders

Ligthart, Lannie, Hottenga, Jouke-Jan, Lewis, Cathryn M., Farmer, Anne E., Craig, Ian W., Breen, Gerome, Willemsen, Gonneke, Vink, Jacqueline M., Middeldorp, Christel M., Byrne, Enda M., Heath, Andrew C., Madden, Pamela A. F., Pergadia, Michele L., Montgomery, Grant W., Martin, Nicholas G., Penninx, Brenda W. J. H., McGuffin, Peter, Boomsma, Dorret I. and Nyholt, Dale R. (2014) Genetic risk score analysis indicates migraine with and without comorbid depression are genetically different disorders. Human Genetics, 133 2: 173-186. doi:10.1007/s00439-013-1370-8


Author Ligthart, Lannie
Hottenga, Jouke-Jan
Lewis, Cathryn M.
Farmer, Anne E.
Craig, Ian W.
Breen, Gerome
Willemsen, Gonneke
Vink, Jacqueline M.
Middeldorp, Christel M.
Byrne, Enda M.
Heath, Andrew C.
Madden, Pamela A. F.
Pergadia, Michele L.
Montgomery, Grant W.
Martin, Nicholas G.
Penninx, Brenda W. J. H.
McGuffin, Peter
Boomsma, Dorret I.
Nyholt, Dale R.
Title Genetic risk score analysis indicates migraine with and without comorbid depression are genetically different disorders
Journal name Human Genetics   Check publisher's open access policy
ISSN 0340-6717
1432-1203
Publication date 2014-02-01
Year available 2013
Sub-type Article (original research)
DOI 10.1007/s00439-013-1370-8
Open Access Status Not yet assessed
Volume 133
Issue 2
Start page 173
End page 186
Total pages 14
Place of publication Heidelberg, Germany
Publisher Springer
Language eng
Abstract Migraine and major depressive disorder (MDD) are comorbid, moderately heritable and to some extent influenced by the same genes. In a previous paper, we suggested the possibility of causality (one trait causing the other) underlying this comorbidity. We present a new application of polygenic (genetic risk) score analysis to investigate the mechanisms underlying the genetic overlap of migraine and MDD. Genetic risk scores were constructed based on data from two discovery samples in which genome-wide association analyses (GWA) were performed for migraine and MDD, respectively. The Australian Twin Migraine GWA study (N = 6,350) included 2,825 migraine cases and 3,525 controls, 805 of whom met the diagnostic criteria for MDD. The RADIANT GWA study (N = 3,230) included 1,636 MDD cases and 1,594 controls. Genetic risk scores for migraine and for MDD were used to predict pure and comorbid forms of migraine and MDD in an independent Dutch target sample (NTR-NESDA, N = 2,966), which included 1,476 MDD cases and 1,058 migraine cases (723 of these individuals had both disorders concurrently). The observed patterns of prediction suggest that the 'pure' forms of migraine and MDD are genetically distinct disorders. The subgroup of individuals with comorbid MDD and migraine were genetically most similar to MDD patients. These results indicate that in at least a subset of migraine patients with MDD, migraine may be a symptom or consequence of MDD.
Formatted abstract
Migraine and major depressive disorder (MDD) are comorbid, moderately heritable and to some extent influenced by the same genes. In a previous paper, we suggested the possibility of causality (one trait causing the other) underlying this comorbidity. We present a new application of polygenic (genetic risk) score analysis to investigate the mechanisms underlying the genetic overlap of migraine and MDD. Genetic risk scores were constructed based on data from two discovery samples in which genome-wide association analyses (GWA) were performed for migraine and MDD, respectively. The Australian Twin Migraine GWA study (N = 6,350) included 2,825 migraine cases and 3,525 controls, 805 of whom met the diagnostic criteria for MDD. The RADIANT GWA study (N = 3,230) included 1,636 MDD cases and 1,594 controls. Genetic risk scores for migraine and for MDD were used to predict pure and comorbid forms of migraine and MDD in an independent Dutch target sample (NTR–NESDA, N = 2,966), which included 1,476 MDD cases and 1,058 migraine cases (723 of these individuals had both disorders concurrently). The observed patterns of prediction suggest that the ‘pure’ forms of migraine and MDD are genetically distinct disorders. The subgroup of individuals with comorbid MDD and migraine were genetically most similar to MDD patients. These results indicate that in at least a subset of migraine patients with MDD, migraine may be a symptom or consequence of MDD.
Keyword Genome-wide association
Major depression
Environmental influences
Young adults
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID ERC-230374
NWO 904-61-193
10-000-1002
MH081802
241944
A7960034
QLG2-CT-2002-01254
AA07535
G0701420
G0701420
G0000647
LSHB-CT-2003-503428
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2014 Collection
 
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