A common variant on chromosome 9p21 affects the risk of myocardial infarction.
The global endemic of cardiovascular diseases calls for improved risk assessment and treatment. Here, we describe an association between myocardial infarction (MI) and a common sequence variant on chromosome 9p21. This study included a total of 4587 cases and 12,767 controls. The identified variant, adjacent to the tumor suppressor genes CDKN2A and CDKN2B, was associated with the disease with high significance. Approximately 21% of individuals in the population are homozygous for this variant, and their estimated risk of suffering myocardial infarction is 1.64 times as great as that of noncarriers. The corresponding risk is 2.02 times as great for early-onset cases. The population attributable risk is 21% for MI in general and 31% for early-onset cases.
Helgadottir
Anna
A
deCODE genetics, Sturlugata 8, IS-101 Reykjavik, Iceland.
Thorleifsson
Gudmar
G
Manolescu
Andrei
A
Gretarsdottir
Solveig
S
Blondal
Thorarinn
T
Jonasdottir
Aslaug
A
Jonasdottir
Adalbjorg
A
Sigurdsson
Asgeir
A
Baker
Adam
A
Palsson
Arnar
A
Masson
Gisli
G
Gudbjartsson
Daniel F
DF
Magnusson
Kristinn P
KP
Andersen
Karl
K
Levey
Allan I
AI
Backman
Valgerdur M
VM
Matthiasdottir
Sigurborg
S
Jonsdottir
Thorbjorg
T
Palsson
Stefan
S
Einarsdottir
Helga
H
Gunnarsdottir
Steinunn
S
Gylfason
Arnaldur
A
Vaccarino
Viola
V
Hooper
W Craig
WC
Reilly
Muredach P
MP
Granger
Christopher B
CB
Austin
Harland
H
Rader
Daniel J
DJ
Shah
Svati H
SH
Quyyumi
Arshed A
AA
Gulcher
Jeffrey R
JR
Thorgeirsson
Gudmundur
G
Thorsteinsdottir
Unnur
U
Kong
Augustine
A
Stefansson
Kari
K
D017668:Age of Onset; D000368:Aged; D016022:Case-Control Studies; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D003324:Coronary Artery Disease / Q000235:genetics; D005260:Female; D019942:Genes, p16; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors