Precision medicine for understudied populations

by Roxana Daneshjou, guest contributor

Precision medicine, which leverages a patient’s genetics to help make medical decisions, has the potential to revolutionize medicine. Its applications are numerous: from predicting who may have an adverse reaction to a medication, to allowing targeted therapies of cancer with particular mutations. In 2015, President Obama’s State of the Union announced an initiative to further our understanding of precision medicine and to build the infrastructure to implement it. An important part of this initiative is building a large diverse research cohort to help discover disease-gene and drug-gene associations. The key word is diverse – because genetic risk factors can be population-specific. In the past, individuals of African, Hispanic, and Middle Eastern ancestry have been understudied. Only by including individuals from all different ancestral backgrounds can we hope to implement precision medicine in an inclusive way.

In 2011, Russ Altman’s research group was pondering the importance of inclusive precision medicine when it became clear that several studies examining the baseline genetic variation across the globe, 1000 Genomes and the International HapMap Project, had an underrepresentation of Middle Eastern populations. As a scientist of Iranian descent who had undergone direct-to-consumer genotyping with 23andMe, I wondered how to make sense of my data when no baseline genetic study of the Iranian population existed. When scientists Dr. Mostafa Ronaghi and Dr. Pardis Sabeti approached Dr. Altman’s group about the idea of creating such a baseline, I was immediately interested. Through the generous support of the PARSA Foundation, we began our journey to create a genetic baseline of the Iranian population.

Our first roadblock appeared when we spent months exploring the feasibility of collecting samples in Iran. Due to the economic sanctions at that time, it turned out that establishing a collaboration with an Iranian university and collecting samples there would be nearly impossible. In the United States, however, the Iranian diaspora has created a sizeable population generally representing the diversity of sub-ethnic groups in Iran.  We turned to this population to collect our samples and conducted high coverage sequencing of 77 healthy individuals. This data can be used for answering some questions about the population’s history and also as a baseline for scientists interested in studying disease in this population.

Since our aim is to enable other scientists to answer important questions about disease risk and treatment in individuals of Iranian ancestry, we are committed to sharing our data. Our website, irangenes.com, already has summary data of population level genetic variants. We’re currently working on uploading all of our genomic data on a secure server so that scientists can submit proposals to use our raw data.  Since the sanctions on Iran were lifted in January 2016, we have corresponded with scientists in Iran who are using our summary data to help advance precision medicine there. We are also working on uploading all of our genomic data to a secure server as a part of the precision medicine initiative so that scientists can submit proposals to use our raw data.

In addition to the medical applications, we were also interested in learning more about the Iranian population’s history through its genetics. Based on our data, the Iranian population is genetically distinct from other Middle Eastern populations. However, it is important to remember that any two humans share 99.9% of their genome. Moreover, as has been seen in previous studies in other populations, the different Iranian sub-ethnic groups have a lot of genetic overlap. Though capturing the breadth of human genetic diversity is important to inclusive precision medicine, these studies also show us that – at our core – we are a singular human family.

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Roxana Daneshjou is an MD/Ph.D. student at Stanford and is supported by the Paul and Daisy Soros Fellowship for New Americans.