Low Levels of Genetic Divergence across Geographically and Linguistically Diverse Populations from India

Ongoing modernization in India has elevated the prevalence of many complex genetic diseases associated with a western lifestyle and diet to near-epidemic proportions. However, although India comprises more than one sixth of the world's human population, it has largely been omitted from genomic surveys that provide the backdrop for association studies of genetic disease. Here, by genotyping India-born individuals sampled in the United States, we carry out an extensive study of Indian genetic variation. We analyze 1,200 genome-wide polymorphisms in 432 individuals from 15 Indian populations. We find that populations from India, and populations from South Asia more generally, constitute one of the major human subgroups with increased similarity of genetic ancestry. However, only a relatively small amount of genetic differentiation exists among the Indian populations. Although caution is warranted due to the fact that United States–sampled Indian populations do not represent a random sample from India, these results suggest that the frequencies of many genetic variants are distinctive in India compared to other parts of the world and that the effects of population heterogeneity on the production of false positives in association studies may be smaller in Indians (and particularly in Indian-Americans) than might be expected for such a geographically and linguistically diverse subset of the human population.

[1]  M. Boehnke,et al.  Accurate inference of relationships in sib-pair linkage studies. , 1997, American journal of human genetics.

[2]  F. Balloux,et al.  Geography predicts neutral genetic diversity of human populations , 2005, Current Biology.

[3]  M. Stoneking,et al.  Genetic structure and affinities among tribal populations of southern India: a study of 24 autosomal DNA markers , 2004, Annals of human genetics.

[4]  S. Hasnain,et al.  Genetic structure of Indian populations based on fifteen autosomal microsatellite loci , 2006, BMC Genetics.

[5]  M. Stoneking,et al.  The northeast Indian passageway: a barrier or corridor for human migrations? , 2004, Molecular biology and evolution.

[6]  Sophie Ancelet,et al.  Bayesian Clustering Using Hidden Markov Random Fields in Spatial Population Genetics , 2006, Genetics.

[7]  P. Donnelly,et al.  Case-control studies of association in structured or admixed populations. , 2001, Theoretical population biology.

[8]  Rui Mei,et al.  Large-scale SNP analysis reveals clustered and continuous patterns of human genetic variation , 2005, Human Genomics.

[9]  M. Feldman,et al.  Genetic Structure of Human Populations , 2002, Science.

[10]  Jerilyn A. Walker,et al.  Genetic variation among world populations: inferences from 100 Alu insertion polymorphisms. , 2003, Genome research.

[11]  B. C. Mishra,et al.  Consortium IGVThe Indian Genome Variation database (IGVdb): a project overview. Hum Genet 118:1-11 , 2005 .

[12]  M. Stephens,et al.  Inference of population structure using multilocus genotype data: linked loci and correlated allele frequencies. , 2003, Genetics.

[13]  Debasis Dash,et al.  The Indian Genome Variation database (IGVdb): a project overview , 2005, Human Genetics.

[14]  N. Saitou,et al.  Phylogenetic relationship of the populations within and around Japan using 105 short tandem repeat polymorphic loci , 2006, Human Genetics.

[15]  Romila Thapar,et al.  A History of India , 1966 .

[16]  V. Kashyap,et al.  Genetic structure of four socio-culturally diversified caste populations of southwest India and their affinity with related Indian and global groups , 2004, BMC Genetics.

[17]  L. Jorde,et al.  Diversity and Divergence Among the Tribal Populations of India , 2005, Annals of human genetics.

[18]  P. Majumder,et al.  Insertion/Deletion Polymorphisms in Tribal Populations of Southern India and Their Possible Evolutionary Implications , 2003, Human biology.

[19]  M. Nei.  Molecular Evolutionary Genetics , 1987 .

[20]  Geoffrey B. Nilsen,et al.  Whole-Genome Patterns of Common DNA Variation in Three Human Populations , 2005, Science.

[21]  J. Mehta,et al.  Malignant coronary artery disease in young asian indians: Thoughts on pathogenesis, prevention, and therapy , 1995, Clinical cardiology.

[22]  M. Stoneking,et al.  Independent Origins of Indian Caste and Tribal Paternal Lineages , 2004, Current Biology.

[23]  M. Hammer,et al.  Genetic Evidence on the Origins of Indian Caste Populations Material Supplemental , 2022 .

[24]  G. Marth,et al.  STRP Screening Sets for the human genome at 5 cM density , 2003, BMC Genomics.

[25]  John S Witte,et al.  Point: population stratification: a problem for case-control studies of candidate-gene associations? , 2002, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[26]  Noah A. Rosenberg,et al.  A General Population-Genetic Model for the Production by Population Structure of Spurious Genotype–Phenotype Associations in Discrete, Admixed or Spatially Distributed Populations , 2006, Genetics.

[27]  C. Snehalatha,et al.  Rising prevalence of NIDDM in an urban population in India , 1997, Diabetologia.

[28]  Rajeev Gupta,et al.  Prevalence of metabolic syndrome in an Indian urban population. , 2004, International journal of cardiology.

[29]  Jeffrey Ross-Ibarra,et al.  Genetic Data Analysis II. Methods for Discrete Population Genentic Data , 2002 .

[30]  C. Uppaluri.  Heart disease and its related risk factors in Asian Indians. , 2002, Ethnicity & disease.

[31]  Sohini Ramachandran,et al.  Support from the relationship of genetic and geographic distance in human populations for a serial founder effect originating in Africa. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[32]  J. Gusella,et al.  Use of cyclosporin a in establishing epstein-barr virus-transformed human lymphoblastoid cell lines , 1984, In Vitro.

[33]  Elad Ziv,et al.  Human population structure and genetic association studies. , 2003, Pharmacogenomics.

[34]  Michael J Bamshad,et al.  Human population genetic structure and inference of group membership. , 2003, American journal of human genetics.

[35]  L. Wasserman,et al.  Genomic control, a new approach to genetic-based association studies. , 2001, Theoretical population biology.

[36]  L. Cavalli-Sforza,et al.  Multilocus genotypes, a tree of individuals, and human evolutionary history. , 1997, American journal of human genetics.

[37]  P. Majumder.  Ethnic populations of India as seen from an evolutionary perspective , 2001, Journal of Biosciences.

[38]  M. Stoneking,et al.  Mitochondrial DNA analysis reveals diverse histories of tribal populations from India , 2003, European Journal of Human Genetics.

[39]  Jeremy Heil,et al.  Human diallelic insertion/deletion polymorphisms. , 2002, American journal of human genetics.

[40]  M P Epstein,et al.  Improved inference of relationship for pairs of individuals. , 2000, American journal of human genetics.

[41]  Hongzhe Li,et al.  Examination of ancestry and ethnic affiliation using highly informative diallelic DNA markers: application to diverse and admixed populations and implications for clinical epidemiology and forensic medicine , 2005, Human Genetics.

[42]  M. Olivier.  A haplotype map of the human genome. , 2003, Nature.

[43]  N. Rosenberg,et al.  Standardized Subsets of the HGDP‐CEPH Human Genome Diversity Cell Line Panel, Accounting for Atypical and Duplicated Samples and Pairs of Close Relatives , 2006, Annals of human genetics.

[44]  M. Bamshad,et al.  Directional migration in the Hindu castes: inferences from mitochondrial, autosomal and Y-chromosomal data , 2004, Human Genetics.

[45]  J. Stephens,et al.  Haplotype Variation and Linkage Disequilibrium in 313 Human Genes , 2001, Science.

[46]  P. Majumder,et al.  Ethnic India: a genomic view, with special reference to peopling and structure. , 2003, Genome research.

[47]  V. Kashyap,et al.  Influence of language and ancestry on genetic structure of contiguous populations: A microsatellite based study on populations of Orissa , 2005, BMC Genetics.

[48]  Jonathan Scott Friedlaender,et al.  A Human Genome Diversity Cell Line Panel , 2002, Science.

[49]  P. Donnelly,et al.  Inference of population structure using multilocus genotype data. , 2000, Genetics.

[50]  P. Majumder,et al.  FUNDAMENTAL GENOMIC UNITY OF ETHNIC INDIA IS REVEALED BY ANALYSIS OF MITOCHONDRIAL DNA , 2000 .

[51]  N. Nanda,et al.  Prevalence of diabetes mellitus and related conditions in Asian Indians living in the United States. , 2004, The American journal of cardiology.

[52]  L. Cardon,et al.  The complex interplay among factors that influence allelic association , 2004, Nature Reviews Genetics.

[53]  M. Feldman,et al.  Clines, Clusters, and the Effect of Study Design on the Inference of Human Population Structure , 2005, PLoS genetics.

[54]  N. Saitou,et al.  The neighbor-joining method: a new method for reconstructing phylogenetic trees. , 1987, Molecular biology and evolution.

[55]  M. Olivier.  A haplotype map of the human genome , 2003, Nature.

[56]  Genetic variation at fifteen microsatellite loci in human populations of india , 2003 .