Expanding genetic research to Indian populations reveals new pathways to disease

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Photo by Ricky Raina on Unsplash
Photo by Ricky Raina on Unsplash

International researchers have discovered new ways genetics can influence the development of cardiometabolic diseases, including obesity, type 2 diabetes and heart disease, by researching 3000 people of Punjabi Sikh ethnicity. The researchers say the incidence of cardiometabolic diseases has been increasing among Sikh populations despite high rates of vegetarianism and low rates of smoking. They say much of what we know about the genetic drivers of these diseases comes from studies done primarily with Europeans. Comparing data from the Punjabi Sikh group with larger genetic studies, the researchers say they were able to find genetic pathways that influence disease risk, including one genetic variant that may protect against heart disease in Indians. They say expanding research to look at more diverse populations provides new opportunities to understand how these diseases develop and look at new ways of treating them.

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From: PLOS

Genetic study in Indians finds new pathways involved in cardiometabolic disease

Study of 3,000 Punjabi Sikhs may yield new targets for treating Type 2 diabetes and other disorders

A study conducted in an Indian population has identified new molecular pathways that contribute to cardiovascular disease, which had not been reported previously in studies of Europeans. Dharambir Sanghera of the University of Oklahoma Health Sciences Center, U.S., led the new study, which was published April 23rd in the open access journal PLOS Medicine.

Worldwide, rates of cardiometabolic disease, which includes obesity, Type 2 diabetes and heart disease, are on the rise, and South Asian people living abroad appear to be especially susceptible. Previous studies have looked for genes that influence the levels of various breakdown products of lipids in the blood and their connection to different diseases, but most of this research has been conducted in people of European ancestry.

In the new study, researchers looked at how genetics influenced the levels of 516 lipid metabolites in the blood of 3,000 Punjabi Sikh individuals, in an effort to better understand how these genetic pathways contribute to disease in different ethnic groups. They compared their findings to previous results from more than 1 million Europeans and 15,000 individuals with Indian ancestry. The team identified new genetic pathways that link specific lipid metabolites to disease. Notably, they confirmed that one metabolite, LPC O-16:0, which is known to be involved with immune cell signaling and inflammation, influences Type 2 diabetes risk. They also identified a genetic variant that may protect Indians from developing heart disease by modulating levels of the metabolite PC 38:4.

These findings offer new insights into the diverse molecular origins of cardiometabolic disease and provide potential pathways to be explored for designing innovative therapies. The researchers conclude that including more non-European participants in this type of research would help in identifying distinct disease subtypes linked to different genetic pathways. These advances would likely be beneficial in clinical practice by enabling more personalized therapies and preventive strategies for people from different backgrounds.

The authors add, “This study reveals new genetic pathways and lipid markers that contribute to type 2 diabetes and heart disease, specifically emphasizing how immune system signaling affects metabolic health. By identifying unique genetic signatures in Asian Indians, the research advocates for ancestry-specific medical approaches to address chronic immuno-vascular conditions in cardiometabolic disease.”

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Study design and outcome summary.
Study design and outcome summary.

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PLOS Medicine
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Organisation/s: University of Oklahoma, USA
Funder: This work was funded by the National Institutes of Health (NIH) grants R01DK082766 and R01DK118427 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (https://www.niddk.nih.gov). DKS, MR, and the Asian Indian Diabetic Heart Study/ Sikh Diabetes Study (AIDHS/SDS) were in part supported by NIH grants, K01TW006087 (https://www.fic.nih.gov), R01DK082766 and R01DK118427 (https://www.niddk.nih. gov), Dr. Geoffrey Altshuler Children’s Hospital Foundation Endowment funds (https://www. ouhealth.com/oklahoma-childrens-hospital- office-of-philanthro), and funding from Presbyterian Health Foundation of Oklahoma (https://www.phfokc.com). CEA, in part, was supported by the Oklahoma Shared Clinical and Translational Resources (U54GM104938) (osctr.ouhsc.edu) with an Institutional Development Award (IDeA) from NIGMS (https://www.nigms.nih.gov). HHG was supported in part by NIH grants R01DK099051 and R01DK118427 (https://www.niddk.nih.gov). RG was supported in part by NIH/R01DK118427 (https://www.niddk.nih.gov).
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