Attempts to replicate genetic associations with schizophrenia in a cohort from north India

Schizophrenia is a chronic, severe, heritable disorder. Genome-wide association studies, conducted predominantly among Caucasians, have indicated > 100 risk alleles, with most significant SNPs on chromosome 6. There is growing interest as to whether these risk alleles are relevant in other ethnic groups as well. Neither an Indian genome-wide association studies nor a systematic replication of GWAS findings from other populations are reported. Thus, we analyzed 32 SNPs, including those associated in the Caucasian ancestry GWAS and other candidate gene studies, in a north Indian schizophrenia cohort (n = 1009 patients; n = 1029 controls) using a Sequenom mass array. Cognitive functioning was also assessed using the Hindi version of the Penn Computerized Neuropsychological Battery in a subset of the sample. MICB (rs6916394) a previously noted Caucasian candidate, was associated with schizophrenia at the p = 0.02 level. One SNP, rs2064430, AHI1 (6q23.3, SZ Gene database SNP) was associated at the p = 0.04 level. Other candidates had even less significance with rs6932590, intergenic (p = 0.07); rs3130615, MICB (p = 0.08); rs6916921, NFKBIL1 (p = 0.08) and rs9273012, HLA-DQA1 (p = 0.06) and haplotypic associations (p = 0.01-0.05) of 6p SNPs were detected. Of note, nominally significant associations with cognitive variables were identified, after covarying for age and diagnostic status. SNPs with p < 0.01 were: rs3130375, with working memory (p = 0.007); rs377763, with sensorimotor (p = 0.004); rs6916921, NFKBIL1 with emotion (p = 0.01). This relative lack of significant positive associations is likely influenced by the sample size and/or differences in the genetic architecture of schizophrenia across populations, encouraging population specific studies to identify shared and unique genetic risk factors for schizophrenia.

CAUCASIANS AND INDIANS EXHIBIT GENETIC DISJUNCTION IN SCHIZOPHRENIA: A tenuous link between schizophrenia's genetic basis in Caucasians and Indians calls for more comprehensive research on the latter. Large-scale analyses of the human genome have identified over a hundred genetic variations associated with schizophrenia; however, these have focused largely on European and North American populations. Researchers led by the University of Delhi's BK Thelma, and Smita Deshpande of the Dr. Ram Manohar Lohia Hospital, India, selected 32 gene variations from past studies to look for similar associations in Indians. Many assays met limited success, though the team found significant correlations between certain variations and specific cognitive hallmarks of schizophrenia. Aside from differences in genetic architecture, the lack of adequate and comparable genetic data on schizophrenia in Indians may contribute to this apparent difference to schizophrenia in Caucasian patients. This shows a clear need for more schizophrenia genetic studies in India.