Format

Send to

Choose Destination
Neuron. 2018 May 16;98(4):743-753.e4. doi: 10.1016/j.neuron.2018.04.014. Epub 2018 May 3.

Common Variant Burden Contributes to the Familial Aggregation of Migraine in 1,589 Families.

Author information

1
Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
2
Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.
3
Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland.
4
Merck Research Laboratories, Merck and Co., Kenilworth, NJ, USA.
5
Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Cologne Center for Genomics, University of Cologne, Cologne, Germany.
6
Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland.
7
Regional State Administrative Agency for Northern Finland, Oulu, Finland.
8
Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland; Division of Pain Medicine, Department of Anesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Finland.
9
Department of Neurology, Central Hospital Central Finland, Jyväskylä.
10
Terveystalo Clinical Research, Turku, Finland.
11
Turku Headache Center, Turku, Finland.
12
Terveystalo, Tampere, Finland.
13
Lääkärikeskus Ikioma, Mikkeli, Finland.
14
Departments of Child Neurology and General Practice, University of Turku, and Turku University Hospital, Turku, Finland.
15
Epilepsy Unit for Children and Adolescents, Helsinki University Hospital, Helsinki, Finland.
16
National Institute for Health and Welfare, Helsinki, Finland.
17
Department of Clinical Chemistry, Fimlab Laboratories, Faculty of Medicine and Life Sciences, University of Tampere, Finland.
18
Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland; Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.
19
Northern Finland Birth Cohorts, Faculty of Medicine, University of Oulu, Oulu, Finland.
20
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
21
Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland.
22
23andMe, Inc., Mountain View, CA, USA.
23
Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland; Public Health, Faculty of Medicine, University of Helsinki, Finland.
24
Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland; Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland.
25
Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland. Electronic address: aarno.palotie@helsinki.fi.

Abstract

Complex traits, including migraine, often aggregate in families, but the underlying genetic architecture behind this is not well understood. The aggregation could be explained by rare, penetrant variants that segregate according to Mendelian inheritance or by the sufficient polygenic accumulation of common variants, each with an individually small effect, or a combination of the two hypotheses. In 8,319 individuals across 1,589 migraine families, we calculated migraine polygenic risk scores (PRS) and found a significantly higher common variant burden in familial cases (n = 5,317, OR = 1.76, 95% CI = 1.71-1.81, p = 1.7 × 10-109) compared to population cases from the FINRISK cohort (n = 1,101, OR = 1.32, 95% CI = 1.25-1.38, p = 7.2 × 10-17). The PRS explained 1.6% of the phenotypic variance in the population cases and 3.5% in the familial cases (including 2.9% for migraine without aura, 5.5% for migraine with typical aura, and 8.2% for hemiplegic migraine). The results demonstrate a significant contribution of common polygenic variation to the familial aggregation of migraine.

KEYWORDS:

GWAS; PRS; disease aggregation; familial aggregation; families; genome-wide association study; hemiplegic migraine; migraine; migraine with aura; polygenic risk score

PMID:
29731251
PMCID:
PMC5967411
[Available on 2019-05-16]
DOI:
10.1016/j.neuron.2018.04.014

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center