Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
24081561
TITLE
Genetic risk score analysis indicates migraine with and without comorbid depression are genetically different disorders.
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.
DATE PUBLISHED
2014 Feb
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2013/07/19
accepted 2013/09/22
aheadofprint 2013/10/01
entrez 2013/10/02 06:00
pubmed 2013/10/02 06:00
medline 2014/03/29 06:00
pmc-release 2015/02/01 00:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Ligthart L Ligthart Lannie L Department of Biological Psychology, VU University, van der Boechorststraat 1, 1081 BT, Amsterdam, The Netherlands, rsl.ligthart@vu.nl.
Hottenga JJ Hottenga Jouke-Jan JJ
Lewis CM Lewis Cathryn M CM
Farmer AE Farmer Anne E AE
Craig IW Craig Ian W IW
Breen G Breen Gerome G
Willemsen G Willemsen Gonneke G
Vink JM Vink Jacqueline M JM
Middeldorp CM Middeldorp Christel M CM
Byrne EM Byrne Enda M EM
Heath AC Heath Andrew C AC
Madden PA Madden Pamela A F PA
Pergadia ML Pergadia Michele L ML
Montgomery GW Montgomery Grant W GW
Martin NG Martin Nicholas G NG
Penninx BW Penninx Brenda W J H BW
McGuffin P McGuffin Peter P
Boomsma DI Boomsma Dorret I DI
Nyholt DR Nyholt Dale R DR
INVESTIGATORS
JOURNAL
VOLUME: 133
ISSUE: 2
TITLE: Human genetics
ISOABBREVIATION: Hum. Genet.
YEAR: 2014
MONTH: Feb
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1432-1203
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Hum Genet
COUNTRY: Germany
ISSNLINKING: 0340-6717
NLMUNIQUEID: 7613873
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Twin Study
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
AA07535 NIAAA NIH HHS United States
AA10249 NIAAA NIH HHS United States
AA13320 NIAAA NIH HHS United States
AA13321 NIAAA NIH HHS United States
AA13326 NIAAA NIH HHS United States
AA14041 NIAAA NIH HHS United States
DA019951 NIDA NIH HHS United States
DA12854 NIDA NIH HHS United States
G0000647 Medical Research Council United Kingdom
G0701420 Medical Research Council United Kingdom
K05 AA017688 NIAAA NIH HHS United States
K08 DA019951 NIDA NIH HHS United States
MH081802 NIMH NIH HHS United States
MH66206 NIMH NIH HHS United States
R01 AA007535 NIAAA NIH HHS United States
R01 AA010249 NIAAA NIH HHS United States
R01 AA013320 NIAAA NIH HHS United States
R01 AA013321 NIAAA NIH HHS United States
R01 AA013326 NIAAA NIH HHS United States
R01 AA014041 NIAAA NIH HHS United States
R01 DA012854 NIDA NIH HHS United States
R01 MH066206 NIMH NIH HHS United States
R01 MH081802 NIMH NIH HHS United States
R56 DA012854 NIDA NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adult
Australia epidemiology
Comorbidity epidemiology
Depressive Disorder, Major psychology
Female psychology
Genetic Testing psychology
Genome-Wide Association Study psychology
Humans psychology
Interviews as Topic psychology
Male psychology
Middle Aged psychology
Migraine Disorders psychology
Multifactorial Inheritance genetics
Netherlands epidemiology
Polymorphism, Single Nucleotide genetics
Risk Factors genetics
Young Adult genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
OTHERID SOURCE
NIHMS528798 [Available on 02/01/15] NLM
PMC3947136 [Available on 02/01/15] NLM