January 9, 2014
The introduction in 2011 of new, highly accurate, non-invasive prenatal genetic tests garnered a significant amount of media attention. Both critics and enthusiasts predicted that the new tests would pave the way for a future in which pregnant women could access large amounts of information about their fetus’ genetic make-up as early as 8 weeks of gestation, following a simple blood test. It isn’t yet clear if or when that future will materialize because the new non-invasive tests use fragments of the fetus’ DNA circulating in the mother’s blood, making it hard to gather a complete picture of the fetus’ genetic make-up. The testing companies are working to expand the tests’ capabilities—and many think it likely that the range of genetic information that the tests can detect will soon expand. For now, though, the first iteration of these tests looks for aneuploidies of chromosomes 21, 13, 18, X and Y.
While public attention has been focused on the new non-invasive prenatal tests, the information that can be accessed using invasive prenatal diagnosis has exploded as a direct result of advances in genetic technology. Currently, fetal cell samples taken during chorionic villus sampling or amniocentesis are karyotyped (the chromosomes are analyzed), and increasingly subjected to genome-wide chromosomal microarray analysis which can reveal far more genetic information about copy number variations (CNVs) in the fetus, including those CNVs associated with increased risk for developing psychiatric, neurological, and/or behavioral conditions. The same CNVs can be associated with a range of neuropsychiatric traits, which can manifest differently in different patients—and these differences are not able to be predicted from the genetic testing results.
A letter in the December 1, 2013 issue of American Journal of Psychiatry describes the incidence in a prenatal sample of copy number variants (CNVs) associated with increased risk for schizophrenia. The authors write that, of the copy number variants identified in a study led by Columbia’s Ron Wapner, “established schizophrenia risk variants accounted for 49% (17 of 35) of the copy number variants of definite clinical significance discovered in 3,822 karyotypically normal pregnancies.” The ability to identify these and similar CNVs through prenatal diagnosis leads the letter authors to predict that “[d]emand for early interventions to reduce such risks is likely to increase.” The authors do not explain what kinds of early interventions they foresee, and for many disorders associated with CNVs detected in these tests, clinically proven, effective interventions are not available. Currently, pregnant women receiving this kind of information following prenatal diagnosis are deciding whether or not to continue with the pregnancy—and if they do continue they are preparing themselves for a child who may have special needs or who is at increased risk for specific diseases or disorders.
As the authors of the AJP letter correctly predict, use of prenatal diagnosis to identify gene variants associated with increased risk for psychiatric disorders like schizophrenia “carries ethical and social implications.” Indeed, these implications are an important focus of the research we are conducting at the Center for Research on the Ethical, Legal and Social Implications of Psychiatric, Neurologic and Behavioral Genetics. Our current research includes a major research project led by Wendy Chung as well as our overarching analysis of the ethical, legal and social implications of PNB genetics more generally.