Epigenetic inheritance and smoking moms

April 20, 2016

A few issues back (October 2015), I took up in this space the topic of “epigenetic inheritance”—the theory that environmental influences can affect genes and be passed on to the next generation. The context was a study that suggested that survivors of the Nazi Holocaust during World War II had passed on to their children genetic changes that predisposed them to stress disorders. The researchers analyzed one region of a gene that has been associated with the regulation of stress hormones. They found chemical “tags” on the same part of this gene in the Holocaust survivors and their children, but not in either generation of control subjects.

Epigenetic inheritance flies in the face of textbook genetics, which holds that genes contained in DNA are the only means for the transfer of biological information from generation to generation. And yet, Gregor Mendel did not know about the presence of genetic tags, and scientists today are only beginning to understand the biology of these chemical influences. Further research may in fact cause geneticists to rewrite the textbooks—and complicate further  the age-old controversy of “nature versus nurture” as well.

Because the research keeps on coming. Recent studies indicate that chronic pain changes the immune system; that there is an epigenetic switch for obesity; and, in research published March 31 in the American Journal of Genetics, that maternal smoking alters fetal DNA.

That’s right. A study of more than 6,000 mothers and their newborn children has solidified earlier evidence that smoking cigarettes while pregnant chemically modifies a fetus’ DNA—mirroring patterns seen in adult smokers. The researchers also identified new development-related genes affected by smoking. Their work suggests a potential explanation for the link between smoking during pregnancy and health complications in children.

“I find it kind of amazing when we see these epigenetic signals in newborns, from in utero exposure, lighting up [no pun intended?] the same genes as an adult’s own cigarette smoking,” says co-senior author Stephanie London, an epidemiologist and physician at the National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health. There’s a lot of overlap. This is a blood-borne exposure to smoking—the fetus isn’t breathing it, but many of the same things are going to be passing through the placenta.”

Links between smoking and chemical modifications to DNA, or methylation, have been found for developing fetuses in smaller studies, but the larger analysis gives scientists more power to uncover patterns. An international team of researchers pooled results from 6,685 newborns and their mothers around the world. Based on questionnaires, mothers were labeled as “sustained smokers” who smoked cigarettes daily throughout most of pregnancy (13 percent), “non-smokers” (62 percent), or those with “any smoking” during pregnancy (25 percent), which captured mothers who were occasional smokers or who quit smoking early on.

To analyze methylation in the newborns’ DNA, researchers collected samples mainly from blood in the umbilical cord after delivery. For the newborns whose mothers fell into the “sustained smoker” category, the research teams identified 6,073 places where the DNA was chemically modified differently than in the “no smoking” newborns. About half of these locations could be tied to a specific gene.

London and her colleagues found that this collection of genes related to lung and nervous system development, smoking-related cancers, birth defects such as cleft lip and palate, and more. “Many signals tied into developmental pathways,” says Bonnie Joubert, an epidemiologist at the NIEHS and a co-first author on the paper. In a separate analysis, many of these DNA modifications were still apparent in older children whose mothers had smoked during pregnancy.

Epigenetics, defined as the regulation of gene expression beyond the primary information encoded by DNA, is established science. The extent of its influence may be far greater than geneticists had imagined.