Searching for genes in complex diseases: lessons from systemic lupus erythematosus

An article appearing last year in the JCI (1) found evidence of a role for the gene for poly(ADP-ribose) polymerase, PARP, in susceptibility to systemic lupus erythematosus (SLE).Two letters now appear in the current issue, one, by Criswell et al. (2), refuting a role of PARP in SLE, and the other, from the original authors, responding to this letter (3).This exchange merits some additional discussion, because it illustrates many of the difficulties faced by researchers searching for genetic factors in complex diseases.