A multicenter study of BRD2 as a risk factor for juvenile myoclonic epilepsy.
OBJECTIVE
Although complex idiopathic generalized epilepsies (IGEs) are recognized to have a significant genetic component, as yet there are no known common susceptibility variants. It has recently been suggested that variation in the BRD2 gene confers increased risk of juvenile myoclonic epilepsy (JME), which accounts for around a quarter of all IGE. Here we examine the association between the candidate causal SNP (the promoter variant rs3918149) and JME in five independent cohorts comprising in total 531 JME cases and 1,390 healthy controls.


METHODS
The strongest candidate causal variant from the original report (rs3918149) was genotyped across all five cohorts. In an effort to identify novel candidate causal polymorphisms, previously unscreened regions of UTR were resequenced.


RESULTS
We observed a significant effect in a small sample recruited in Britain (genotype p = 0.001, allele p = 0.001), a borderline significant effect in a sample recruited in Ireland and no association in larger samples of German, Australian, and Indian populations. There was no association with other common forms of epilepsy or any other clear candidate casual variants in or near the BRD2 region.


CONCLUSIONS
The replication of an effect in the British cohort and suggestive evidence from that recruited in Ireland but lack of replication from the larger German, Australian, and Indian cohorts is surprising and difficult to explain. Further replication in carefully matched populations is required. Results presented here do not, however, support a strong effect for susceptibility to JME across populations of European descent.
Cavalleri
Gianpiero L
GL
The Department of Clinical Neurological Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland.
Walley
Nicole M
NM
Soranzo
Nicole
N
Mulley
John
J
Doherty
Colin P
CP
Kapoor
Ashish
A
Depondt
Chantal
C
Lynch
John M
JM
Scheffer
Ingrid E
IE
Heils
Armin
A
Gehrmann
Anne
A
Kinirons
Peter
P
Gandhi
Sonia
S
Satishchandra
Parthasarathy
P
Wood
Nicholas W
NW
Anand
Anuranjan
A
Sander
Thomas
T
Berkovic
Samuel F
SF
Delanty
Norman
N
Goldstein
David B
DB
Sisodiya
Sanjay M
SM
D016022:Case-Control Studies; D015331:Cohort Studies; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005828:Genetics, Population; D005838:Genotype; D006801:Humans; D020190:Myoclonic Epilepsy, Juvenile / Q000453:epidemiology / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012307:Risk Factors; D014157:Transcription Factors; D006113:United Kingdom / Q000453:epidemiology; D044465:White People / Q000235:genetics / Q000706:statistics & numerical data; D000092468:Bromodomain Containing Proteins
D017346:Protein Serine-Threonine Kinases; D014157:Transcription Factors; C098415:BRD2 protein, human; D000092468:Bromodomain Containing Proteins