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Family and twin studies show that genetic variation influences suicidal behavior, but do not indicate specific genes. We investigated the relationship between genetic variation and suicide attempt by screening 250 genetic markers using transmission disequilibrium test (TDT) analysis. Analysis of 77 triplets (suicide attempters and both their parents), indicated that gene-variants in, or adjacent to, the sodium channel, voltage gated, type VIII, alpha polypeptide (SCN8A) (P = 0.008), vesicle-associated membrane protein 4 (VAMP4) (P = 0.004), and prenylated Rab acceptor 1 (RABAC1) (P = 0.006) genes are over-transmitted in suicide attempt. Replication in a separate sample, consisting of 190 triplets, confirmed the exploratory data for the SCN8A (P = 0.005) and VAMP4 (P = 0.019) genes, but failed to confirm the data for the RABAC1 gene. Our results indicate that genetic variation in the SCN8A and VAMP4 genes may contribute to risk for suicide attempt, possibly through alterations in neural conduction.