Which genes cause heart attack and do any of these operate outside of known risk factors for heart disease?

Since 2006, our laboratory has studied early-onset MI (heart attack which occurs in men prior to their 51st birthday and in women prior to their 61st birthday) because MI that occurs early in life has a greater genetic basis.  The Kathiresan laboratory working with an international group of collaborators has led three genome-wide association studies (GWAS) for the MI or coronary artery disease. Results are summarized below.

Genome-wide association studies for MI or coronary artery disease led by the Kathiresan laboratory

Study

Number of MI cases

Number of MI-free controls

Year Published

Journal

Number of DNA sequence variants discovered

Myocardial Infarction Genetics Consortium (MIGen)

2,967

3,075

2009

Nature Genetics

9

Coronary ARtery DIsease Genome wide Replication and Meta-analysis (CARDIoGRAM) Consortium.

22,233

64,762

2011

Nature Genetics

25

CARDIoGRAMPlusC4D Consortium

63,746

130,681

2013

Nature Genetics

45

Of the 45 DNA sequence variants most highly associated with MI and coronary artery disease, fifteen are related to known risk factors. Ten relate to plasma LDL cholesterol or lipoprotein(a), demonstrating the central role for LDL in leading to atherosclerosis. Four variants relate to blood pressure.  One at the lipoprotein lipase gene relates to both plasma triglycerides and HDL cholesterol.  Remarkably, the remaining 30 or 2/3 of the genetic discoveries do NOT relate to known risk factors.  These seem to be many contributors to atherosclerosis in humans that were not previously appreciated.