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Value of Diversity in Study Populations Highlighted at ASHG

Diverse crowd

LOS ANGELES ­– Diverse ancestry groups in study populations enabled findings that would not have been otherwise possible, according to data presented at last week's American Society of Human Genetics (ASHG) annual conference in Los Angeles.

The lack of diversity in study populations, ranging from basic research on cell lines to clinical trials, biases the benefits of scientific findings to people of largely European descent. Results presented at the conference provided evidence for the biomedical relevance of greater diversity.

In a meta-analysis of Global Biobank Analysis Initiative data, Juulia Partanen of the Institute for Molecular Medicine Finland identified novel alleles associated with idiopathic pulmonary fibrosis (IPF).

Partanen and her colleagues analyzed over 11,000 IPF patients and over 1 million population controls comprising six ancestry groups from 13 biobanks around the globe. They found 25 genome-wide significant IPF loci, seven of which were new and only one of which she said would have been identified had the analysis been restricted to Europeans.

Another of the newly discovered loci is specific to East Asian populations, three are associated with lung function, and two are known to be differentially expressed in IPF. Applying fine-mapping to FinnGen data suggested that coding variants at three loci were likely causal of IPF, highlighting an unreported missense variant in KIF15. Furthermore, seven of the 25 IPF loci are also associated with COVID-19 hospitalization, highlighting the utility of integrating genetic data with electronic health records. Partanen's study was recently published in Cell Genomics.

Konstantinos Hatzikotoulas of the Institute of Translational Genomics at the Helmholtz Center Munich in Germany aggregated genome-wide association study (GWAS) summary statistics for over 2.5 million individuals from five major ancestry groups to better understand biological pathways driving type 2 diabetes (T2D) susceptibility.

Hatzikotoulas and his colleagues identified 611 loci, 145 of which had not been previously reported. Loci associated with insulin production and processing had larger effects on T2D in East Asian ancestry populations, while those associated with obesity had more pronounced effects in populations of European ancestry.

Dovetailing recent studies investigating differences in genetic inflammatory bowel disease (IBD) risk between European, African-American, and Ashkenazi Jewish ancestry groups, Ruize Liu of Massachusetts General Hospital analyzed over 14,000 IBD cases among East Asian and European populations. She uncovered 26 IBD-associated coding variants in East Asians, 13 of which had never been reported in either ancestry group. The results point toward new IBD-associated loci and identified two new IBD genes for the first time in known loci, which may facilitate target modulation in future drug discovery.

Finally, Katherine Aracena of the University of Chicago presented data on genetic, epigenetic, and transcriptional changes in primary macrophages derived from individuals of European or African ancestry before and after influenza A infection.

Aracena's results, currently available as a preprint on BioRxiv, showed that epigenetic profiles are predictive of individuals' transcriptional responses to infection, and that ancestry-associated differences in those transcriptional responses accompany epigenetic differences between ancestry groups. Of potential biomedical relevance, she found that greater amounts of African ancestry corresponded more strongly to inflammation-associated gene expression signatures both before and after flu infection.