How do your 20,000 genes determine so many wildly different traits? They multitask. By Sarah Kaplan May 17 at 8:05 AM  

 (Washington Post illustration by Rachel Orr; Images from iStock) You probably wouldn't be surprised if a scientist told you that your genes influence when you hit puberty, how tall you are, what your BMI will be and whether you're likely to develop male pattern baldness. But what if he said that the same gene could hold sway over all four things? That finding comes from a study published Monday in the journal Nature Genetics. Using data from dozens of genome-wide association studies (big scans of complete sets of DNA from many thousands of people), researchers at the New York Genome Center and the genetic analysis company 23andMe found examples of single "multitasking" genes that influence diverse and sometimes seemingly disparate traits. The scientists say that the links

they uncovered could help researchers understand how certain genes work, and figure out better ways of treating some of the health problems they might control. “Most studies tend to go one disease at a time," said Joseph Pickrell, a professor at Columbia University and the New York Genome Center's lead investigator on the project. "But if we can try to make these sorts of connections between what you might think of as unrelated traits ... that gives us another angle of attack to understand the connections between these different diseases." To start, Pickrell and his team sought out genome-wide association studies (GWAS) identifying particular genetic variants associated with 42 different traits. Many had to do with diseases (for example, studies that linked certain genes to the risk of developing Alzheimer's or type 2 diabetes) and other personal health traits (body mass index, blood type, cholesterol levels). But the researchers also looked at traits that don't often get studied, like chin dimples and the tendency to sneeze when you see the sun (yes, the "photic sneeze reflex" is an actual genetic condition, and Rachel totally has it). Data from 23andMe was useful for studying those kinds of traits, Pickrell said: a scientist can't exactly go to the NIH and ask for funding to find the gene for sneezing in sunlight. (Well, maybe he could ask. But he probably wouldn't get any.) But the biotech company collects that kind of information anyway for its personal genome tests. Seventeen of the studies surveyed for the paper were conducted by 23andMe researchers using the company's database of more than 1 million users. The biotech company has come under scrutiny in recent years. In 2013, the Food and Drug Administration warned the company to stop giving customers health-related results out of concern that the tests might be inaccurate or misleading in influencing medical decisions. The company has since revamped its test, with input from regulators, to offer what it says are more scientifically sound results on a smaller group of diseases. Pickrell said he's confident in the 23andMe studies, adding that an outside GWAS about the onset of menarche (the fancy term for periods) in girls gave very similar results to the one done by the biotech company's researchers. Armed with all these studies, Pickrell and his team then cross-referenced them to identify more than 300 spots on the genome that were associated with more than one trait. In some cases, predisposition to two different diseases could be definitively linked to a particular genetic variation — for example, a variant that controls the transportation of metals around cells was associated

with increased risk for schizophrenia and decreased risk for Parkinson's disease. "That tells us that heavy metal transport is important for all those diseases in different ways," Pickrell said. It should also inform researchers trying to develop treatments for patients with either disease, he added: "If you can understand why [they are linked] in principle, you could start to think about ... if I’m developing a drug for schizophrenia will it have an adverse effect on a person with Parkinson's?" In other cases, researchers weren't able to nail down the particular genetic variant that linked traits. But usually it made sense that the traits would be associated with one another. For example, height, age of puberty, BMI and baldness — all associated with the same spot on the genome — are influenced by hormones. It seems likely that there's a gene somewhere controlling the release of hormones that affect all these other things. Likewise, many immune system-related problems, including asthma, allergies and susceptibility to childhood ear infections, were clustered around a particular spot on the genome. Of course, the links between genes and diseases aren't one to one. Having a particular variant may predispose you to allergies, or Parkinson's, or sneezing when the sun comes out, or even some combination of the three, but it doesn't determine your destiny. Genes are complicated. But the study could help disentangle some of that complexity. "It’s a smart use of available data,” Matthew Rockman, a biologist at New York University who was not involved in the study, told the magazine the Scientist about Pickrell's work. "Revealing commonalities among different kinds of diseases could point towards unexpected avenues of therapy, [even if that] is still very distant," Rockman said.