title: Comparative analyses of genetic risk prediction methods reveal extreme diversity of genetic predisposition to nonalcoholic fatty liver disease (NAFLD) among ethnic populations of India.
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.
authors.affiliation: National Institute of Biomedical Genomics, Netaji Subhas Sanatorium (T. B. Hospital), Kalyani 741 251, India. pb1@nibmg.ac.in.
authors.forename: Ankita
authors.initials: A
authors.lastname: Chatterjee
authors.forename: Analabha
authors.initials: A
authors.lastname: Basu
authors.forename: Abhijit
authors.initials: A
authors.lastname: Chowdhury
authors.forename: Kausik
authors.initials: K
authors.lastname: Das
authors.forename: Neeta
authors.initials: N
authors.lastname: Sarkar-Roy
authors.forename: Partha P
authors.initials: PP
authors.lastname: Majumder
authors.forename: Priyadarshi
authors.initials: P
authors.lastname: Basu
mesh_terms: D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007194:India; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics*; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment
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