Scientists using the latest tools to scan the human genome must pay attention to ancestry when analyzing and interpreting their results

Dr. Gregersen studies rheumatoid arthritis, and in 2004 his team discovered an important risk gene called PTPN22. In the US, the disease associated variant of PTPN22 is present in about eight-to-10 percent of the population. Since the vast majority of Caucasians living in the US had ancestors who once lived in Europe, the few thousand genetic markers identified by Dr. Seldin were used to track those with European origins. They tested the DNA from hundreds of people in Europe and found that there was an enormous difference in the frequency of the risk variant for PTPN22, according to whether a person’s ancestors are from southern vs. northern Europe. In Southern Italy, for instance, only about three percent of the population had this specific PTPN22 allele. Moving north into Sweden, about 12-to-15 percent of the population carries this variant. This variant increases the risk for rheumatoid arthritis and a number of other autoimmune conditions. With these same genetic markers in hand – so called “ancestry informative makers,” or “AIMs.” the scientists went after their US sample, asking whether these markers could be used to identify where a person’s ancestors were from – even if the subjects themselves did not know this information. Indeed, the study showed that they could. In November 2008, Dr. Gregersen presented findings from their work at the American Society of Human Genetics meetings in Philadelphia. The team showed that these markers distinguish ancestry more precisely than any tool available today. The genetic information is so specific that one could look at genes from an Asian individual living in New York and tell whether their ancestors migrated from Cambodia, Japan, Korea or any other country in Asia. Going back to the PTPN22 gene, this team of investigators found that it is not a risk factor for rheumatoid arthritis in the Asian population. That means that if Asians were mixed into a genetic study on rheumatoid arthritis it could greatly skew the findings. “When you put thousands of these markers together, you get a probability of who comes from Sweden or Southern Italy,” said Dr. Gregersen.