Gaurav Bhatia (l), Alkes Price

Gaurav Bhatia (l), Alkes Price

HSPH study suggests natural selection at work in certain disease-related genes

September 29, 2011

A new study led by Harvard School of Public Health (HSPH) researchers implies that, among three closely related African-ancestry populations, natural selection is at work in genes related to malaria and bladder and gastric cancers. Ultimately, the research could help shed light on the role of natural selection in disease resistance.

The study, “Genome-wide Comparison of African-Ancestry Populations from CARe and Other Cohorts Reveals Signals of Natural Selection,” was published in the Sept. 9, 2011 issue of the American Journal of Human Genetics.

The study marks the first analysis of population differences on genome-wide data from African populations. These populations have been understudied despite the fact that they harbor a wealth of genetic diversity.

To conduct their research, Gaurav Bhatia, a graduate student in the Harvard-MIT Health, Science, and Technology program, and Alkes Price, assistant professor of statistical genetics at HSPH, along with collaborators from the CARe consortium and other groups, developed novel methods that allow for the simultaneous analysis of multiple populations. This helped improve their ability to detect selection and to establish which population was subject to the selective pressure.

“Looking at closely related populations is significant because there are not many genetic differences between them. So when there is a difference, you know that something interesting is going on,” said Bhatia.

Bhatia and Price studied newly available data from more than 12,000 African Americans, Nigerians, and Gambians, as well as from a smaller cohort of Chinese and Japanese individuals. Because the African populations are genetically close, it allowed the researchers to more robustly demonstrate evidence of natural selection in genes than if they’d studied more genetically distant groups. The Asian group was included as part of a second analysis of natural selection in closely related populations.

Finding signals for natural selection can help uncover the genetics of disease resistance, according to Price. Understanding how someone’s genes affect disease susceptibility can help identify new treatments and improve existing treatments.

Previous research has indicated the presence of natural selection related to malaria-related genes, and the new research strongly confirms that finding. Furthermore, the evidence of natural selection at a gene associated with bladder and gastric cancer—in both the African and Asian populations studied—had not been previously reported. This finding could indicate a similar environmental pressure in East Asia and West Africa that has driven natural selection.

The researchers’ finding—that natural selection appears to be at work in certain disease-related genes—is significant because it can help broaden understanding of how populations respond genetically to environmental pressures such as infectious disease. “Many genes related to infectious disease and changes in environment have been uncovered through studies of natural selection,” said Price. “We aimed to contribute to that effort with this research.”

–Karen Feldscher

photo: Aubrey LaMedica