Insight in glioma susceptibility through an analysis of 6p22.3, 12p13.33-12.1, 17q22-23.2 and 18q23 SNP genotypes in familial and non-familial glioma

Yanhong Liu, Beatrice S. Melin, Preetha Rajaraman, Zhaoming Wang, Martha Linet, Sanjay Shete, Christopher I. Amos, Ching C. Lau, Michael E. Scheurer, Spiridon Tsavachidis, Georgina N. Armstrong, Richard S. Houlston, Fay J. Hosking, Elizabeth B. Claus, Jill Barnholtz-Sloan, Rose Lai, Dora Il'yasova, Joellen Schildkraut, Siegal Sadetzki, Christoffer JohansenJonine L. Bernstein, Sara H. Olson, Robert Brian Jenkins, Daniel La Chance, Nicholas A. Vick, Margaret Wrensch, Faith Davis, Bridget J. McCarthy, Ulrika Andersson, Patricia A. Thompson, Stephen Chanock, Melissa L. Bondy

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Abstract

The risk of glioma has consistently been shown to be increased twofold in relatives of patients with primary brain tumors (PBT). A recent genome-wide linkage study of glioma families provided evidence for a disease locus on 17q12-21.32, with the possibility of four additional risk loci at 6p22.3, 12p13.33-12.1, 17q22-23.2, and 18q23. To identify the underlying genetic variants responsible for the linkage signals, we compared the genotype frequencies of 5,122 SNPs mapping to these five regions in 88 glioma cases with and 1,100 cases without a family history of PBT (discovery study). An additional series of 84 familial and 903 non-familial cases were used to replicate associations. In the discovery study, 12 SNPs showed significant associations with family history of PBT (P < 0.001). In the replication study, two of the 12 SNPs were confirmed: 12p13.33-12.1 PRMT8 rs17780102 (P = 0.031) and 17q12-21.32 SPOP rs650461 (P = 0.025). In the combined analysis of discovery and replication studies, the strongest associations were attained at four SNPs: 12p13.33-12.1 PRMT8 rs17780102 (P = 0.0001), SOX5 rs7305773 (P = 0.0001) and STKY1 rs2418087 (P = 0.0003), and 17q12-21.32 SPOP rs6504618 (P = 0.0006). Further, a significant gene-dosage effect was found for increased risk of family history of PBT with these four SNPs in the combined data set (P trend <1.0 × 10 -8). The results support the linkage finding that some loci in the 12p13.33-12.1 and 17q12-q21.32 may contribute to gliomagenesis and suggest potential target genes underscoring linkage signals.

Original languageEnglish (US)
Pages (from-to)1507-1517
Number of pages11
JournalHuman Genetics
Volume131
Issue number9
DOIs
StatePublished - Sep 2012

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Glioma
Single Nucleotide Polymorphism
Brain Neoplasms
Genotype
Gene Dosage
Genome
Genes

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

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Insight in glioma susceptibility through an analysis of 6p22.3, 12p13.33-12.1, 17q22-23.2 and 18q23 SNP genotypes in familial and non-familial glioma. / Liu, Yanhong; Melin, Beatrice S.; Rajaraman, Preetha; Wang, Zhaoming; Linet, Martha; Shete, Sanjay; Amos, Christopher I.; Lau, Ching C.; Scheurer, Michael E.; Tsavachidis, Spiridon; Armstrong, Georgina N.; Houlston, Richard S.; Hosking, Fay J.; Claus, Elizabeth B.; Barnholtz-Sloan, Jill; Lai, Rose; Il'yasova, Dora; Schildkraut, Joellen; Sadetzki, Siegal; Johansen, Christoffer; Bernstein, Jonine L.; Olson, Sara H.; Jenkins, Robert Brian; La Chance, Daniel; Vick, Nicholas A.; Wrensch, Margaret; Davis, Faith; McCarthy, Bridget J.; Andersson, Ulrika; Thompson, Patricia A.; Chanock, Stephen; Bondy, Melissa L.

In: Human Genetics, Vol. 131, No. 9, 09.2012, p. 1507-1517.

Research output: Contribution to journalArticle

Liu, Y, Melin, BS, Rajaraman, P, Wang, Z, Linet, M, Shete, S, Amos, CI, Lau, CC, Scheurer, ME, Tsavachidis, S, Armstrong, GN, Houlston, RS, Hosking, FJ, Claus, EB, Barnholtz-Sloan, J, Lai, R, Il'yasova, D, Schildkraut, J, Sadetzki, S, Johansen, C, Bernstein, JL, Olson, SH, Jenkins, RB, La Chance, D, Vick, NA, Wrensch, M, Davis, F, McCarthy, BJ, Andersson, U, Thompson, PA, Chanock, S & Bondy, ML 2012, 'Insight in glioma susceptibility through an analysis of 6p22.3, 12p13.33-12.1, 17q22-23.2 and 18q23 SNP genotypes in familial and non-familial glioma', Human Genetics, vol. 131, no. 9, pp. 1507-1517. https://doi.org/10.1007/s00439-012-1187-x
Liu, Yanhong ; Melin, Beatrice S. ; Rajaraman, Preetha ; Wang, Zhaoming ; Linet, Martha ; Shete, Sanjay ; Amos, Christopher I. ; Lau, Ching C. ; Scheurer, Michael E. ; Tsavachidis, Spiridon ; Armstrong, Georgina N. ; Houlston, Richard S. ; Hosking, Fay J. ; Claus, Elizabeth B. ; Barnholtz-Sloan, Jill ; Lai, Rose ; Il'yasova, Dora ; Schildkraut, Joellen ; Sadetzki, Siegal ; Johansen, Christoffer ; Bernstein, Jonine L. ; Olson, Sara H. ; Jenkins, Robert Brian ; La Chance, Daniel ; Vick, Nicholas A. ; Wrensch, Margaret ; Davis, Faith ; McCarthy, Bridget J. ; Andersson, Ulrika ; Thompson, Patricia A. ; Chanock, Stephen ; Bondy, Melissa L. / Insight in glioma susceptibility through an analysis of 6p22.3, 12p13.33-12.1, 17q22-23.2 and 18q23 SNP genotypes in familial and non-familial glioma. In: Human Genetics. 2012 ; Vol. 131, No. 9. pp. 1507-1517.
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title = "Insight in glioma susceptibility through an analysis of 6p22.3, 12p13.33-12.1, 17q22-23.2 and 18q23 SNP genotypes in familial and non-familial glioma",
abstract = "The risk of glioma has consistently been shown to be increased twofold in relatives of patients with primary brain tumors (PBT). A recent genome-wide linkage study of glioma families provided evidence for a disease locus on 17q12-21.32, with the possibility of four additional risk loci at 6p22.3, 12p13.33-12.1, 17q22-23.2, and 18q23. To identify the underlying genetic variants responsible for the linkage signals, we compared the genotype frequencies of 5,122 SNPs mapping to these five regions in 88 glioma cases with and 1,100 cases without a family history of PBT (discovery study). An additional series of 84 familial and 903 non-familial cases were used to replicate associations. In the discovery study, 12 SNPs showed significant associations with family history of PBT (P < 0.001). In the replication study, two of the 12 SNPs were confirmed: 12p13.33-12.1 PRMT8 rs17780102 (P = 0.031) and 17q12-21.32 SPOP rs650461 (P = 0.025). In the combined analysis of discovery and replication studies, the strongest associations were attained at four SNPs: 12p13.33-12.1 PRMT8 rs17780102 (P = 0.0001), SOX5 rs7305773 (P = 0.0001) and STKY1 rs2418087 (P = 0.0003), and 17q12-21.32 SPOP rs6504618 (P = 0.0006). Further, a significant gene-dosage effect was found for increased risk of family history of PBT with these four SNPs in the combined data set (P trend <1.0 × 10 -8). The results support the linkage finding that some loci in the 12p13.33-12.1 and 17q12-q21.32 may contribute to gliomagenesis and suggest potential target genes underscoring linkage signals.",
author = "Yanhong Liu and Melin, {Beatrice S.} and Preetha Rajaraman and Zhaoming Wang and Martha Linet and Sanjay Shete and Amos, {Christopher I.} and Lau, {Ching C.} and Scheurer, {Michael E.} and Spiridon Tsavachidis and Armstrong, {Georgina N.} and Houlston, {Richard S.} and Hosking, {Fay J.} and Claus, {Elizabeth B.} and Jill Barnholtz-Sloan and Rose Lai and Dora Il'yasova and Joellen Schildkraut and Siegal Sadetzki and Christoffer Johansen and Bernstein, {Jonine L.} and Olson, {Sara H.} and Jenkins, {Robert Brian} and {La Chance}, Daniel and Vick, {Nicholas A.} and Margaret Wrensch and Faith Davis and McCarthy, {Bridget J.} and Ulrika Andersson and Thompson, {Patricia A.} and Stephen Chanock and Bondy, {Melissa L.}",
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T1 - Insight in glioma susceptibility through an analysis of 6p22.3, 12p13.33-12.1, 17q22-23.2 and 18q23 SNP genotypes in familial and non-familial glioma

AU - Liu, Yanhong

AU - Melin, Beatrice S.

AU - Rajaraman, Preetha

AU - Wang, Zhaoming

AU - Linet, Martha

AU - Shete, Sanjay

AU - Amos, Christopher I.

AU - Lau, Ching C.

AU - Scheurer, Michael E.

AU - Tsavachidis, Spiridon

AU - Armstrong, Georgina N.

AU - Houlston, Richard S.

AU - Hosking, Fay J.

AU - Claus, Elizabeth B.

AU - Barnholtz-Sloan, Jill

AU - Lai, Rose

AU - Il'yasova, Dora

AU - Schildkraut, Joellen

AU - Sadetzki, Siegal

AU - Johansen, Christoffer

AU - Bernstein, Jonine L.

AU - Olson, Sara H.

AU - Jenkins, Robert Brian

AU - La Chance, Daniel

AU - Vick, Nicholas A.

AU - Wrensch, Margaret

AU - Davis, Faith

AU - McCarthy, Bridget J.

AU - Andersson, Ulrika

AU - Thompson, Patricia A.

AU - Chanock, Stephen

AU - Bondy, Melissa L.

PY - 2012/9

Y1 - 2012/9

N2 - The risk of glioma has consistently been shown to be increased twofold in relatives of patients with primary brain tumors (PBT). A recent genome-wide linkage study of glioma families provided evidence for a disease locus on 17q12-21.32, with the possibility of four additional risk loci at 6p22.3, 12p13.33-12.1, 17q22-23.2, and 18q23. To identify the underlying genetic variants responsible for the linkage signals, we compared the genotype frequencies of 5,122 SNPs mapping to these five regions in 88 glioma cases with and 1,100 cases without a family history of PBT (discovery study). An additional series of 84 familial and 903 non-familial cases were used to replicate associations. In the discovery study, 12 SNPs showed significant associations with family history of PBT (P < 0.001). In the replication study, two of the 12 SNPs were confirmed: 12p13.33-12.1 PRMT8 rs17780102 (P = 0.031) and 17q12-21.32 SPOP rs650461 (P = 0.025). In the combined analysis of discovery and replication studies, the strongest associations were attained at four SNPs: 12p13.33-12.1 PRMT8 rs17780102 (P = 0.0001), SOX5 rs7305773 (P = 0.0001) and STKY1 rs2418087 (P = 0.0003), and 17q12-21.32 SPOP rs6504618 (P = 0.0006). Further, a significant gene-dosage effect was found for increased risk of family history of PBT with these four SNPs in the combined data set (P trend <1.0 × 10 -8). The results support the linkage finding that some loci in the 12p13.33-12.1 and 17q12-q21.32 may contribute to gliomagenesis and suggest potential target genes underscoring linkage signals.

AB - The risk of glioma has consistently been shown to be increased twofold in relatives of patients with primary brain tumors (PBT). A recent genome-wide linkage study of glioma families provided evidence for a disease locus on 17q12-21.32, with the possibility of four additional risk loci at 6p22.3, 12p13.33-12.1, 17q22-23.2, and 18q23. To identify the underlying genetic variants responsible for the linkage signals, we compared the genotype frequencies of 5,122 SNPs mapping to these five regions in 88 glioma cases with and 1,100 cases without a family history of PBT (discovery study). An additional series of 84 familial and 903 non-familial cases were used to replicate associations. In the discovery study, 12 SNPs showed significant associations with family history of PBT (P < 0.001). In the replication study, two of the 12 SNPs were confirmed: 12p13.33-12.1 PRMT8 rs17780102 (P = 0.031) and 17q12-21.32 SPOP rs650461 (P = 0.025). In the combined analysis of discovery and replication studies, the strongest associations were attained at four SNPs: 12p13.33-12.1 PRMT8 rs17780102 (P = 0.0001), SOX5 rs7305773 (P = 0.0001) and STKY1 rs2418087 (P = 0.0003), and 17q12-21.32 SPOP rs6504618 (P = 0.0006). Further, a significant gene-dosage effect was found for increased risk of family history of PBT with these four SNPs in the combined data set (P trend <1.0 × 10 -8). The results support the linkage finding that some loci in the 12p13.33-12.1 and 17q12-q21.32 may contribute to gliomagenesis and suggest potential target genes underscoring linkage signals.

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