The Complex Interplay of Genes and Environment
Youssef Idaghdour, NYUAD assistant professor of Biology studies how one's environment can be a vital factor in genetic expression.

The Complex Interplay of Genes and Environment

Youssef Idaghdour's "eureka moment" on the old issue of nature vs. nurture came when he was back in his native Morocco, examining genetic expression in a small sample of Berber individuals for his dissertation.

But his interest in genetics started with birds, not people. "I'm a bird-watcher," Idaghdour said cheerfully.

After earning a Bachelor of Science at the University of Agadir, he worked in a wildlife conservation center where houbara birds were bred in captivity. The work's focus on issues of genetic diversity led him toward genomics and a Master of Science in molecular genetics at the University of Leicester, where he worked in the laboratory in which Sir Alec Jeffreys had discovered the process known as genetic finger-printing. Idaghdour did his Ph.D. at North Carolina State University on a Fulbright Scholarship, before becoming a postdoctoral fellow at the Sainte-Justine Research Center in Montreal, Canada.

In his office at NYU Abu Dhabi's Center for Science and Engineering, he recounted reading a study while he was in North Carolina doing research on free-range and captive wolves. The study found that while the two groups' genetic makeup was similar, the main difference in whether certain genes were turned on or off appeared to be related to the animals' status as captive or free. Environment, it seemed, was a vital factor in which genes were expressed.

To test this hypothesis in humans, Idaghdour returned to Morocco in 2006 and studied blood samples from Amazigh, or Berber, individuals, some living the ancient nomadic life, some mountain farmers, and some city-dwellers from the coast — but all with strong genetic similarities. As he reported in his doctoral dissertation, as much as a third of all genes expressed in blood were "found to be differentially expressed among lifestyles."

Biological processes, Idaghdour said, are complex; there are multiple steps from the simple gene to the phenotype, the observable characteristics that result from the combination of genotype and environment. One of the first key steps, he summarized, is the transcriptome — the sum of the products of genes actively expressed at a given time in an individual. His Berber subjects were found to have dramatic transcriptome variations among the groups.

A larger follow-up study on Amazigh and Arab populations, conducted in 2008 by Idaghdour, replicated the findings of the first study and demonstrated the major influence of lifestyle and geography on gene expression.

Genes protect you against or predispose you to complex diseases, while the environment is more influential in triggering the disease.

Youssef Idaghdour, NYUAD assistant professor of Biology

In other words, Idaghdour explained, "the real answer to the question of 'nature-vs.-nurture' is not either-or, but a combination. Interaction is the key word in what I'm doing." In layman's terms, he said, the basic idea is that "for complex disease such as diabetes, cancer, and asthma, where and how you live are major determinants of the aspects of your health. But genes define one's baseline risk." That is, genes protect you against or predispose you to complex diseases, while the environment is more influential in triggering the disease.

Idaghdour is still analyzing the data from his subsequent project, looking at the risk of cardiovascular disease in a sample of 1,000 people in Montreal, Quebec City, and the rural Saguenay region, all in Canada's Quebec province. Those findings will, he hopes, cast more light on the nature of "gene-environment interactions."

But it's a big job. With 20,000 genes in the human genome, not to mention mutations, the number of conceivable combinations with environmental factors is formidable.

Idaghdour's next research effort focuses specifically on the Arabian Peninsula, where diabetes is a serious public health challenge, especially among the region's residents whose diet and lifestyle have changed dramatically in just one or two generations. "The prevalence of diabetes here is striking," said Idaghdour and "must be caused by both genetics and environment together."

He's hoping to work with the NYUAD Public Health Research Center on a detailed study of Emiratis, measuring the way environment can alter gene expression in ways related to the disease. And for his upcoming NYUAD projects, the University's High Performance Computer will be needed.

Ask Idaghdour where research such as this is going and he speaks of the ultimate promise of "personalized" medicine: "In the US alone," he noted, "more than 100,000 people die every year from the side effects of prescribed drugs."

Detailed genomic analysis, coupled with a good understanding of the genotype-phenotype relationships, incorporating knowledge about environmental effects, may open an important door: it will help us to understand how each individual will respond to a given treatment — and will also help to identify prognostic markers that could predict an individual's medical problems in advance.

And just in case all that is not enough, Idaghdour also reserves some time and energy for a related labor of love, one that recalls his early days in wildlife biology: he's planning to collaborate with NYUAD Associate Professor of Biology John Burt in working to understand the genetic basis of thermal adaptation in corals.

This article originally appeared in NYUAD's 2013-14 Research Report (13MB PDF).