Association study of neuregulin-1 gene polymorphisms in a North Indian schizophrenia sample.
BACKGROUND
Neuregulin-1 (NRG1) gene polymorphisms have been proposed as risk factors for several common disorders. Associations with cognitive variation have also been tested. With regard to schizophrenia (SZ) risk, studies of Caucasian ancestry samples indicate associations more consistently than East Asian samples, suggesting heterogeneity. To exploit the differences in linkage disequilibrium (LD) structure across ethnic groups, we conducted a SZ case-control study (that included cognitive evaluations) in a sample from the north Indian population.


METHODS
NRG1 variants (n=35 SNPs, three microsatellite markers) were initially analyzed among cases (DSM IV criteria, n=1007) and controls (n=1019, drawn from two groups) who were drawn from the same geographical region in North India. Nominally significant associations with SZ were next analyzed in relation to neurocognitive measures estimated with a computerized neurocognitive battery in a subset of the sample (n=116 cases, n=170 controls).


RESULTS
Three variants and one microsatellite showed allelic association with SZ (rs35753505, rs4733263, rs6994992, and microsatellite 420M9-1395, p≤0.05 uncorrected for multiple comparisons). A six marker haplotype 221121 (rs35753505-rs6994992-rs1354336-rs10093107-rs3924999-rs11780123) showed (p=0.0004) association after Bonferroni corrections. Regression analyses with the neurocognitive measures showed nominal (uncorrected) associations with emotion processing and attention at rs35753505 and rs6994992, respectively.


CONCLUSIONS
Suggestive associations with SZ and SZ-related neurocognitive measures were detected with two SNPs from the NRG1 promoter region in a north Indian cohort. The functional role of the alleles merits further investigation.
Department of Genetics, University of Delhi South campus, Benito Juarez Road, New Delhi - 110 021, India; C.B. Patel Research Centre, Vile Parle (West), Mumbai, India.
Prachi
P
Kukshal
Triptish
T
Bhatia
A M
AM
Bhagwat
Raquel E
RE
Gur
Ruben C
RC
Gur
Smita N
SN
Deshpande
Vishwajit L
VL
Nimgaonkar
B K
BK
Thelma
D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D015331:Cohort Studies; D005006:Ethnicity / Q000235:genetics; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D007194:India / Q000208:ethnology; D007231:Infant, Newborn; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D020890:Neuregulin-1 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012559:Schizophrenia / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D055815:Young Adult
D020890:Neuregulin-1