Evaluation of the established non-MHC multiple sclerosis loci in an Indian population

Pandit, Lekha; Ban, Masashi; Sawcer, Stephen; Singhal, Bhim; Nair, Shyam K.; Radhakrishnan, Kurupath; Shetty, Rajesh; Misri, Z K; Hegde, Suresh; Bhat, Irruvathur Gopalakrishna

doi:10.1177/1352458510384011

Cited by 42 publications

(46 citation statements)

References 20 publications

(12 reference statements)

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“…In a study of this size and considering 96 variants, we would anticipate seeing up to five apparently reversed effects by chance alone. A similar low frequency of apparently reversed signals was seen in our previous African American study (Isobe et al, 2013) and also in our study of European multiple sclerosis variants in an Indian data set (Pandit et al, 2011). Although such allele flipping could theoretically have resulted from unusual population-based differences in allele frequencies (Lin et al, 2007;Zaykin and Shibata, 2008;Clarke and Cardon, 2010), no such differences are apparent in the 1000 Genomes data set (The 1000 Genomes Project Consortium, 2010), where the minor allele for these four SNPs is the same in both populations.…”

Section: à5supporting

confidence: 83%

An ImmunoChip study of multiple sclerosis risk in African Americans

Isobe

Madireddy

Khankhanian

et al. 2015

Brain

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*These authors contributed equally to this work.The aims of this study were: (i) to determine to what degree multiple sclerosis-associated loci discovered in European populations also influence susceptibility in African Americans; (ii) to assess the extent to which the unique linkage disequilibrium patterns in African Americans can contribute to localizing the functionally relevant regions or genes; and (iii) to search for novel African American multiple sclerosis-associated loci. Using the ImmunoChip custom array we genotyped 803 African American cases with multiple sclerosis and 1516 African American control subjects at 130 135 autosomal single nucleotide polymorphisms. We conducted association analysis with rigorous adjustments for population stratification and admixture. Of the 110 non-major histocompatibility complex multiple sclerosis-associated variants identified in Europeans, 96 passed stringent quality control in our African American data set and of these, 470% (69) showed over-representation of the same allele amongst cases, including 21 with nominally significant evidence for association (one-tailed test P 5 0.05). At a further eight loci we found nominally significant association with an alternate correlated risk-tagging single nucleotide polymorphism from the same region. Outside the regions known to be associated in Europeans, we found seven potentially associated novel candidate multiple sclerosis variants (P 5 10 À 4 ), one of which (rs2702180) also showed nominally significant evidence for association (one-tailed test P = 0.034) in an independent second cohort of 620 African American cases and 1565 control subjects. However, none of these novel associations reached genome-wide significance (combined P = 6.3 Â 10 À 5 ). Our data demonstrate substantial overlap between African American and European multiple sclerosis variants, indicating common genetic contributions to multiple sclerosis risk.

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Section: à5supporting

confidence: 83%

An ImmunoChip study of multiple sclerosis risk in African Americans

Isobe

Madireddy

Khankhanian

et al. 2015

Brain

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“…In our previously published study of limited power, CD6 gene associated SNP had shown a trend of association. [16] Our recently published replication study on 110 European risk variants provides evidence that many if not all the MS risk variants identified in populations of European ancestry are likely to also be risk variants in the South Asian population. This study hypothesized that B cells and certain immunoglobulins might play an important role in the pathogenesis of MS in South Asian and other Asian populations in comparison to European MS patients.…”

Section: Discussionmentioning

confidence: 99%

“…SNP genotyping was performed on an ABI7500 real-time polymerase chain reaction (PCR) genotyping platform using predesigned TaqMan SNP genotyping assays (Applied Biosystems Inc., Foster City, CA, USA) as described earlier. [16] In short, 4 μl of normalized genomic DNA (5 ng/ul) was aliquoted to the bottom surface of a MicroAmp ® Optical 96-Well Reaction Plate. The DNA sample was dried down completely by evaporation.…”

Section: Methodsmentioning

confidence: 99%

“…[15] An earlier study of 197 patients and controls had shown nominal association with two variants, rs12708716, and rs763361 related to CLEC 16A and CD226 genes, respectively. [16] A replication study of 110 European risk variants has been recently conducted among Indians. [17] In this study, two-thirds of the tested variants (72/109) showed over-representation of European risk allele in South Asian cases ( P < 0.0003).…”

Section: Introductionmentioning

confidence: 99%

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CD6 gene polymorphism rs17824933 is associated with multiple sclerosis in Indian population

D'Cunha¹,

Pandit²,

Malli³

2016

Ann Indian Acad Neurol

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Background:Multiple sclerosis (MS) prevalence has increased worldwide. The known genetic association for MS in the west has not been studied in detail in nonwhite populations and particularly Indians.Objective:The objective of this study was to evaluate some known genetic variations outside the major histocompatibility complex (MHC) region associated with MS in patients of Indian origin.Materials and Methods:We investigated 10 gene-associated single nucleotide polymorphisms (SNP's) outside the MHC region in 300 patients and 720 unrelated controls. Genotyping was performed on an ABI7500 real-time polymerase chain reaction genotyping platform using predesigned TaqMan SNP genotyping assays.Results:CD6 gene associated SNP (rs17824933) showed significant association with MS (P = 4.2 × 10−5, odds ratio [OR] = 2.24, confidence interval (CI) = 1.51–3.33). A modest association was also noted for TMEM39A rs1132200 (P = 0.023, OR = 1.41, CI = 1.05–1.91) and IL2RA rs2104286 (P = 0.04, OR = 1.3, CI = 1.006–1.67). In the remaining SNPs, the allele frequencies were overexpressed in patients when compared to healthy controls.Conclusion:Our data illustrate the similarity in risk association between Indian and European populations for MS.

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“…Furthermore, investigation among them showed that except one study [14], almost all of them suggested that C allele is associated with high risk of MS [7]. IL7Ra rs6897932 SNP is located in exon 6 which encodes integral membrane domain of the receptor, while rs6897932 SNP causes skipping at this site which leads to more soluble form of protein.…”

Section: Discussionmentioning

confidence: 99%

Association between CD127 Gene Polymorphism and Susceptibility to Multiple Sclerosis

Alsahebfosoul¹

2016

SOJI

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Evaluation of the established non-MHC multiple sclerosis loci in an Indian population

Abstract: Although the power of this study was limited, our preliminary data suggest that disease susceptibility genes in MS in the Indian population may be similar to those of western populations.

Cited by 42 publications

References 20 publications

An ImmunoChip study of multiple sclerosis risk in African Americans

An ImmunoChip study of multiple sclerosis risk in African Americans

CD6 gene polymorphism rs17824933 is associated with multiple sclerosis in Indian population

Association between CD127 Gene Polymorphism and Susceptibility to Multiple Sclerosis

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