US newborn genomic sequencing trial publishes first findings

A whole-genome sequencing trial for newborns in the US has published its initial results, detecting a genetic childhood-onset condition in almost 10 percent of babies.

The BabySeq Project pilot study, which involved sequencing the DNA of 159 newborns, revealed unexpected genetic childhood-onset disease risks in 15 cases (9.4 per cent). However, ambiguous results were uncovered in five cases (3.1 percent), which did not give doctors any actionable information.

'Genomic sequencing has the ability to simultaneously analyse thousands of genes that are known to cause disease. But the specificity and sensitivity of genetics tests are uncertain and relatively low, and not all of the diseases that we may find are treatable,' said Dr Alan Beggs, director of the Manton Center for Orphan Disease Research at Boston Children's Hospital, one of the principal investigators for BabySeq.

The trial additionally uncovered useful information on risks of adult-onset conditions, carrier status for recessive diseases and genetic variants affecting how a person will respond to medicines. Of the 159 newborns, 127 were healthy at birth and 32 required intensive care treatment, but not necessarily for genetic disorders.

As well as revealing potentially useful medical information, the test also raises ethical questions. In particular with adult-onset genetic conditions, the results of testing affect other family members beyond the individual whose genome has been sequenced.

In this study, a risk of hereditary colorectal and/or breast cancer was found in three of 85 newborns for whom parents provided additional consent to test for diseases that manifest later in life. 'In this case, it alerted the parents that they should also get tested because they were the ones who had more imminent risk,' said Dr Beggs.

Additionally, of the 159 tested newborns, 140 (88 percent) were found to be carriers of pathological genetic variants, which means that their children would develop the disease if the other parent carried the same variant. Results of testing for carrier status may affect their reproductive choices of the newborns' parents and also of their own partners in adult life.

Many parents found the prospect of knowing genomic information about their newborns' an unappealing prospect. The 159 cases in this study made up only 6.7 percent of the 3860 eligible families that had been approached to enrol in this study. Reasons for declining enrolment included lack of interested in research, concerns about privacy and insurance, as well as finding out ambiguous results or information about untreatable diseases.

The study was published in the American Journal of Human Genetics.