Skip to main content
SpringerLink
Log in

Comparative analyses of genetic risk prediction methods reveal extreme diversity of genetic predisposition to nonalcoholic fatty liver disease (NAFLD) among ethnic populations of India

  • RESEARCH ARTICLE
  • Published:
Journal of Genetics Aims and scope Submit manuscript

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a distinct pathologic condition characterized by a disease spectrum ranging from simple steatosis to steato-hepatitis, cirrhosis and hepatocellular carcinoma. Prevalence of NAFLD varies in different ethnic groups, ranging from 12% in Chinese to 45% in Hispanics. Among Indian populations, the diversity in prevalence is high, ranging from 9% in rural populations to 32% in urban populations, with geographic differences as well. Here, we wished to find out if this difference is reflected in their genetic makeup. To date, several candidate genes and a few genomewide association studies (GWAS) have been carried out, and many associations between single nucleotide polymorphisms (SNPs) and NAFLD have been observed. In this study, the risk allele frequencies (RAFs) of NAFLD-associated SNPs in 20 Indian ethnic populations (376 individuals) were analysed. We used two different measures for calculating genetic risk scores and compared their performance. The correlation of additive risk scores of NAFLD for three Hapmap populations with their weighted mean prevalence was found to be high (R 2=0.93). Later we used this method to compare NAFLD risk among ethnic Indian populations. Based on our observation, the Indian caste populations have high risk scores compared to Caucasians, who are often used as surrogate and similar to Indian caste population in disease gene association studies, and is significantly higher than the Indian tribal populations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  • Amarapurkar D., Kamani P., Patel N., Gupte P., Kumar P., Agal S., et al. 2007 Prevalence of nonalcoholic fatty liver disease: population based study. Ann. Hepatol. 6, 161–163.

    PubMed  Google Scholar 

  • Angulo P. and Lindor K. D. 2002 Non-alcoholic fatty liver disease. J. Gastroenterol. Hepatol. 17, 186–190.

    Article  Google Scholar 

  • Bajaj S., Nigam P., Luthra A., Pandey R. M., Kondal D., Bhatt S. P., et al. 2009 A case-control study on insulin resistance, metabolic co-variates and prediction score in non-alcoholic fatty liver disease. Indian J. Med. Res. 129, 285–292.

    CAS  PubMed  Google Scholar 

  • Bamshad M., Kivisild T., Watkins W. S., Dixon M. E., Ricker C. E., Rao B. B., et al. 2001 Genetic evidence on the origins of Indian caste populations. Genome Res. 11, 994–1004.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Basu A., Mukherjee N., Roy S., Sengupta S., Banerjee S., Chakraborty M., et al. 2003 Ethnic India: a genomic view, with special reference to peopling and structure. Genome Res. 13, 2277–2290.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Browning J. D., Szczepaniak L. S., Dobbins R., Nuremberg P., Horton J. D., Cohen J. C., et al. 2004 Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 40, 1387–1395.

    Article  PubMed  Google Scholar 

  • Cohen J. C., Horton J. D. and Hobbs H. H. 2011 Human fatty liver disease: old questions and new insights. Science 332, 1519–1523.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Corona E., Chen R., Sikora M., Morgan A. A., Patel C. J., Ramesh A., et al. 2013 Analysis of the genetic basis of disease in the context of worldwide human relationships and migration. PLoS Genet. 9, e1003447.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Das K., Das K., Mukherjee P. S., Ghosh A., Ghosh S., Mridha A. R., et al. 2010 Non-obese population in a developing country has a high prevalence of nonalcoholic fatty liver and significant liver disease. Hepatology 51, 1593–1602.

    Article  CAS  PubMed  Google Scholar 

  • Duseja A. 2010 Nonalcoholic fatty liver disease in India – a lot done, yet more required! Indian J. Gastroenterol. 29, 217–225.

    Article  PubMed  Google Scholar 

  • Eguchi Y., Hyogo H., Ono M., Mizuta T, Ono N., Fujimoto K., et al. 2012 Prevalence and associated metabolic factors of nonalcoholic fatty liver disease in the general population from 2009 to 2010 in Japan: a multicenter large retrospective study. J. Gastroenterol. 47, 586–595.

    Article  CAS  PubMed  Google Scholar 

  • Fan J. G., Zhu J., Li X. J., Chen L., Lu Y. S., Li L., et al. 2005 Fatty liver and the metabolic syndrome among Shanghai adults. J. Gastroenterol. Hepatol. 20, 1825–1832.

    Article  PubMed  Google Scholar 

  • Guthery S. L., Salisbury B. A., Pungliya M. S., Stephens J. C. and Bamshad M. 2007 The structure of common genetic variation in United States populations. Am. J. Hum. Genet. 81, 1221–1231.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hancock A. M., Witonsky D. B., Alkorta-Aranburu G., Beall C. M., Gebremedhin A., Sukernik R., et al. 2011 Adaptations to climate-mediated selective pressures in humans. PLoS Genet. 7, e1001375.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hernaez R. 2011 Genetic factors associated with the presence and progression of nonalcoholic fatty liver disease: A narrative review. Gastroenterol. Hepatol. 35, 32–41.

  • Indian Genome Variation Consortium 2008 Genetic landscape of the people of India: a canvas for disease gene exploration. J. Genet. 87, 3–20.

    Article  Google Scholar 

  • Jimba S., Nakagami T., Takahashi M., Wakamatsu T., Hirota Y., Iwamoto Y. and Wasada T. 2005 Prevalence of non-alcoholic fatty liver disease and its association with impaired glucose metabolism in Japanese adults. Diabet. Med. 22, 1141–1145.

    Article  CAS  PubMed  Google Scholar 

  • Majumder P. P. 1998 People of India: Biological diversity and affinities. Evol. Anthropol. 6, 100–110.

    Article  Google Scholar 

  • Mohan V., Farooq S., Deepa M., Ravikumar R. and Pitchumoni C. . -. 1667emS. 2009 Prevalence of non-alcoholic fatty liver disease in urban south Indians in relation to different grades of glucose intolerance and metabolic syndrome. Diabetes Res. Clin. Pract. 84, 84–91.

    Article  CAS  PubMed  Google Scholar 

  • Myles S., Davison D., Barrett J., Stoneking M. and Timpson N. 2008 Worldwide population differentiation at disease-associated SNPs. BMC Med Genomics 1, 22.

  • Nei M. 1978 The theory of genetic distance and evolution of human races. Jap. J. Human Genet. 23, 341–369.

    Article  CAS  Google Scholar 

  • Omagari K., Kadokawa Y. and Masuda J. 2002 Fatty liver in non-alcoholic non-overweight Japanese adults: incidence and clinical characteristics. J. Gastroenterol. Hepatol. 17, 1098– 1105.

    Article  PubMed  Google Scholar 

  • Pemberton T. J., Sandefur C. I, Jakobsson M. and Rosenberg N. A. 2009. Sequence determinants of human microsatellite variability. BMC Genomics 10, 612.

  • Reich D., Thangaraj K., Patterson N., Price A. L. and Singh L. 2009 Reconstructing Indian population history. Nature 461, 489–494.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Roychoudhury S., Roy S., Basu A., Banerjee R., Vishwanathan H., Usha Rani M. V., et al. 2001 Genomic structures and population histories of linguistically distinct tribal groups of India. Hum. Genet. 109, 339–350.

    Article  CAS  PubMed  Google Scholar 

  • Schwimmer J. B., Celedon M. A., Lavine J. E., Salem R., Campbell N., Schork N. J., et al. 2009 Heritability of nonalcoholic fatty liver disease. Gastroenterology 136, 1585–1592.

    Article  PubMed Central  PubMed  Google Scholar 

  • Shen L., Fan J. G., Shao Y., Zeng M. D., Wang J. R., Luo G. H., et al. 2003 Prevalence of nonalcoholic fatty liver among administrative officers in Shanghai: an epidemiological survey. World J. Gastroenterol. 9, 1106–1110.

    PubMed  Google Scholar 

  • Singh S. P., Nayak S., Swain M., Rout N., Mallik R. N., Agrawal O., et al. 2004 Prevalence of nonalcoholic fatty liver disease in coastal eastern India: a preliminary ultrasonographic survey. Indian J. Gastroenterol. 25, 76–79.

    Google Scholar 

  • Torres D. M. and Harrison S. A 2008 Diagnosis and therapy of nonalcoholic steatohepatitis. Gastroenterology 134, 1682–1698.

    Article  CAS  PubMed  Google Scholar 

  • Wilfred de Alwis N. M. and Day C. P. 2008 Genes and nonalcoholic fatty liver disease. Curr. Diab. Rep. 8, 156–163.

    Article  PubMed  Google Scholar 

  • Williams R. 2006 Global challenges in liver disease. Hepatology 44, 521–526.

    Article  PubMed  Google Scholar 

  • Young J. H., Chang Y. P., Kim J. D., Chretien J. P., Klag M. J., Levine M. A., et al. 2005 Differential susceptibility to hypertension is due to selection during the out-of-Africa expansion. PLoS Genet. 1, e82.

    Article  PubMed Central  PubMed  Google Scholar 

  • Zhou Y. -J., Li Y. -Y., Nie Y. -Q., Ma J. X., Lu L. G., Shi S. L., et al. 2007 Prevalence of fatty liver disease and its risk factors in the population of South China. World J. Gastroenterol. 13, 6419–6424.

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to thank all individuals throughout India who have participated in this study. A Chatterjee is supported by a fellowship from the Council of Scientific and Industrial Research fellowship. We would also like to thank Dr. Ankur Mukherjee for guidance and suggestions. The work was sponsored by an NIBMG internal grant.

Author information

Authors and Affiliations

  1. National Institute of Biomedical Genomics, Netaji Subhas Sanatorium (T. B. Hospital), Kalyani, 741 251, India

    ANKITA CHATTERJEE, ANALABHA BASU, NEETA SARKAR-ROY, PARTHA P. MAJUMDER & PRIYADARSHI BASU

  2. Institute of Post Graduate Medical Education and Research, J. C. Bose Road, Kolkata, 700 020, India

    ABHIJIT CHOWDHURY & KAUSIK DAS

  3. Biomedical Genomics Center, PG Polyclinic Building, Kolkata, 700 020, India

    ABHIJIT CHOWDHURY & PRIYADARSHI BASU

Authors
  1. ANKITA CHATTERJEE
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. ANALABHA BASU
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. ABHIJIT CHOWDHURY
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. KAUSIK DAS
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. NEETA SARKAR-ROY
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. PARTHA P. MAJUMDER
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. PRIYADARSHI BASU
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to PRIYADARSHI BASU.

Additional information

[Chatterjee A., Basu A., Chowdhury A., Das K., Sarkar-Roy N., Majumder P. P. and Basu P. 2015 Comparative analyses of genetic risk prediction methods reveal extreme diversity of genetic predisposition to nonalcoholic fatty liver disease (NAFLD) among ethnic populations of India. J. Genet. 94, xx–xx]

Electronic supplementary material

Below is the link to the electronic supplementary material.

(PDF 0.99 MB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

CHATTERJEE, A., BASU, A., CHOWDHURY, A. et al. Comparative analyses of genetic risk prediction methods reveal extreme diversity of genetic predisposition to nonalcoholic fatty liver disease (NAFLD) among ethnic populations of India. J Genet 94, 105–113 (2015). https://doi.org/10.1007/s12041-015-0494-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12041-015-0494-0

Keywords

Search

Navigation