Niraj Doshi

A study looking at Non-Alcoholic Fatty Liver Disease in Trivandrum, India.

Medical Student Essay Prize

“A Genome-Wide Association Study of Non-Alcoholic Fatty Liver Disease in Trivandrum, India.”

The Trivandrum NAFLD cohort comprises 2222 adults were recruited from across Kerala in South India. Cases were defined as participants with evidence of fatty infiltration of the liver on ultrasound scanning. Controls were defined as participants with no evidence of fatty infiltration using the same technique. Extensive historical,
dietary, anthropometric, and biochemical measures were available from all included participants. Genomic DNA was available from 1118 participants and was extracted
in Trivandrum, before genotyping in London, with rigorous quality control applied
to all data.

Findings from the study showed that genetic risk loci robustly associated with the development and progression of NAFLD in European/East Asian populations are not associated with disease susceptibility in South Asians. This, coupled with additional findings concerning lack of associations in loci previously associated with serum enzyme activities, suggests there may be divergence in the genetic risk profile for
developing NAFLD in the South Asian population, compared with others. These
findings may have significant implications for identifying individuals at risk of the
condition and for potential therapeutic targeting.

“Overcoming the technical and conceptual challenges that I faced, and using analytical techniques not previously used by my research group to solve issues, was extremely rewarding. I feel confident that these skills and experiences will stand me in good stead for continuing computational research in this field.”

Why did you choose this project?

‘Although non-alcoholic fatty liver disease (NAFLD) is fast becoming a public health
emergency, there is currently little public awareness about the condition. Certain
populations (such as those in South Asia) appear to be more susceptible to NAFLD
and its associated complications, with the burden of liver disease increasing by 46%
between 1980 and 2010, in low and middle-income countries such as India,
Pakistan, and Bangladesh. At the same time, there is a paucity of high-quality
research into the genetics of diseases in ethnic minority populations compared to

‘I am passionate about redressing this balance; doing so is imperative for ensuring
health equality and reducing disparities in our understanding of disease risk in
different populations. Additionally, being from a South Asian background, I feel
privileged to have undertaken the first genome-wide association study (GWAS) in
liver disease in this ethnic group. Having had no prior experience in the fields of
hepatology, genetics, and bioinformatics, the learning curve was extremely steep.
However, I managed to carry out all stages of this genome-wide association study
(GWAS) with a great amount of independence.’

"I am extremely grateful to Guts UK and Dr Falk for their generosity in awarding me
this prize and helping to raise awareness of the need for research into metabolic liver
disease. The results of this study will help to improve our understanding of the
processes underlying the development of NAFLD, and facilitate further research into
how this disease may be detected at an earlier stage. It will also shed light on targets
for new drugs, many of which are being developed to target specific genetic
pathways.’ ‘Being recognised for my contribution to this work has inspired me to
continue research in this field, and I will now be working to replicate my findings in
other cohorts of South Asian ancestry. I would also like to thank my supervisors,
for allowing me to work on this project and always offering me their
unwavering support."

- Niraj Doshi

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