Estimating the heritability of colorectal cancer

Shuo Jiao, Ulrike Peters, Sonja Berndt, Hermann Brenner, Katja Butterbach, Bette J. Caan, Christopher S. Carlson, Andrew T. Chan, Jenny Chang-Claude, Stephen Chanock, Keith R. Curtis, David Duggan, Jian Gong, Tabitha A. Harrison, Richard B. Hayes, Brian E. Henderson, Michael Hoffmeister, Laurence N. Kolonel, Loic Le Marchand, John D. PotterAnja Rudolph, Robert E. Schoen, Daniela Seminara, Martha L. Slattery, Emily White, Li Hsu

Research output: Contribution to journalArticle

Abstract

A sizable fraction of colorectal cancer (CRC) is expected to be explained by heritable factors, with heritability estimates ranging from 12 to 35% twin and family studies. Genome-wide association studies (GWAS) have successfully identified a number of common single-nucleotide polymorphisms (SNPs) associated with CRC risk. Although it has been shown that these CRC susceptibility SNPs only explain a small proportion of the genetic risk, it is not clear how much of the heritability these SNPs explain and how much is left to be detected by other, yet to be identified, common SNPs. Therefore, we estimated the heritability of CRC under different scenarios using Genome-Wide Complex Trait Analysis in the Genetics and Epidemiology of Colorectal Cancer Consortium including 8025 cases and 10 814 controls. We estimated that the heritability explained by known common CRC SNPs identified inGWASwas 0.65% (95% CI:0.3-1%; P = 1.11 × 10-16), whereas the heritability explained byallcommonSNPswasat least 7.42% (95%CI: 4.71-10.12%;P = 8.13 × 10-8), suggesting thatmany common variants associated with CRC risk remain to be detected. Comparing the heritability explained by the common variants with that from twin and family studies, a fraction of the heritability may be explained by other genetic variants, such as rare variants. In addition, our analysis showed that the gene 3 smoking interaction explained a significant proportionof theCRCvariance (P = 1.26 × 10-2). Insummary, our results suggest that known CRC SNPs only explain a small proportion of the heritability and more common SNPs have yet to be identified.

Original languageEnglish (US)
Article numberddu087
Pages (from-to)3898-3905
Number of pages8
JournalHuman Molecular Genetics
Volume23
Issue number14
DOIs
StatePublished - 2014
Externally publishedYes

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Colorectal Neoplasms
Single Nucleotide Polymorphism
Twin Studies
Molecular Epidemiology
Genome-Wide Association Study
Smoking
Genome
Genes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology
  • Medicine(all)

Cite this

Jiao, S., Peters, U., Berndt, S., Brenner, H., Butterbach, K., Caan, B. J., ... Hsu, L. (2014). Estimating the heritability of colorectal cancer. Human Molecular Genetics, 23(14), 3898-3905. [ddu087]. https://doi.org/10.1093/hmg/ddu087

Estimating the heritability of colorectal cancer. / Jiao, Shuo; Peters, Ulrike; Berndt, Sonja; Brenner, Hermann; Butterbach, Katja; Caan, Bette J.; Carlson, Christopher S.; Chan, Andrew T.; Chang-Claude, Jenny; Chanock, Stephen; Curtis, Keith R.; Duggan, David; Gong, Jian; Harrison, Tabitha A.; Hayes, Richard B.; Henderson, Brian E.; Hoffmeister, Michael; Kolonel, Laurence N.; Marchand, Loic Le; Potter, John D.; Rudolph, Anja; Schoen, Robert E.; Seminara, Daniela; Slattery, Martha L.; White, Emily; Hsu, Li.

In: Human Molecular Genetics, Vol. 23, No. 14, ddu087, 2014, p. 3898-3905.

Research output: Contribution to journalArticle

Jiao, S, Peters, U, Berndt, S, Brenner, H, Butterbach, K, Caan, BJ, Carlson, CS, Chan, AT, Chang-Claude, J, Chanock, S, Curtis, KR, Duggan, D, Gong, J, Harrison, TA, Hayes, RB, Henderson, BE, Hoffmeister, M, Kolonel, LN, Marchand, LL, Potter, JD, Rudolph, A, Schoen, RE, Seminara, D, Slattery, ML, White, E & Hsu, L 2014, 'Estimating the heritability of colorectal cancer', Human Molecular Genetics, vol. 23, no. 14, ddu087, pp. 3898-3905. https://doi.org/10.1093/hmg/ddu087
Jiao S, Peters U, Berndt S, Brenner H, Butterbach K, Caan BJ et al. Estimating the heritability of colorectal cancer. Human Molecular Genetics. 2014;23(14):3898-3905. ddu087. https://doi.org/10.1093/hmg/ddu087
Jiao, Shuo ; Peters, Ulrike ; Berndt, Sonja ; Brenner, Hermann ; Butterbach, Katja ; Caan, Bette J. ; Carlson, Christopher S. ; Chan, Andrew T. ; Chang-Claude, Jenny ; Chanock, Stephen ; Curtis, Keith R. ; Duggan, David ; Gong, Jian ; Harrison, Tabitha A. ; Hayes, Richard B. ; Henderson, Brian E. ; Hoffmeister, Michael ; Kolonel, Laurence N. ; Marchand, Loic Le ; Potter, John D. ; Rudolph, Anja ; Schoen, Robert E. ; Seminara, Daniela ; Slattery, Martha L. ; White, Emily ; Hsu, Li. / Estimating the heritability of colorectal cancer. In: Human Molecular Genetics. 2014 ; Vol. 23, No. 14. pp. 3898-3905.
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abstract = "A sizable fraction of colorectal cancer (CRC) is expected to be explained by heritable factors, with heritability estimates ranging from 12 to 35{\%} twin and family studies. Genome-wide association studies (GWAS) have successfully identified a number of common single-nucleotide polymorphisms (SNPs) associated with CRC risk. Although it has been shown that these CRC susceptibility SNPs only explain a small proportion of the genetic risk, it is not clear how much of the heritability these SNPs explain and how much is left to be detected by other, yet to be identified, common SNPs. Therefore, we estimated the heritability of CRC under different scenarios using Genome-Wide Complex Trait Analysis in the Genetics and Epidemiology of Colorectal Cancer Consortium including 8025 cases and 10 814 controls. We estimated that the heritability explained by known common CRC SNPs identified inGWASwas 0.65{\%} (95{\%} CI:0.3-1{\%}; P = 1.11 × 10-16), whereas the heritability explained byallcommonSNPswasat least 7.42{\%} (95{\%}CI: 4.71-10.12{\%};P = 8.13 × 10-8), suggesting thatmany common variants associated with CRC risk remain to be detected. Comparing the heritability explained by the common variants with that from twin and family studies, a fraction of the heritability may be explained by other genetic variants, such as rare variants. In addition, our analysis showed that the gene 3 smoking interaction explained a significant proportionof theCRCvariance (P = 1.26 × 10-2). Insummary, our results suggest that known CRC SNPs only explain a small proportion of the heritability and more common SNPs have yet to be identified.",
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AU - Berndt, Sonja

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AU - Butterbach, Katja

AU - Caan, Bette J.

AU - Carlson, Christopher S.

AU - Chan, Andrew T.

AU - Chang-Claude, Jenny

AU - Chanock, Stephen

AU - Curtis, Keith R.

AU - Duggan, David

AU - Gong, Jian

AU - Harrison, Tabitha A.

AU - Hayes, Richard B.

AU - Henderson, Brian E.

AU - Hoffmeister, Michael

AU - Kolonel, Laurence N.

AU - Marchand, Loic Le

AU - Potter, John D.

AU - Rudolph, Anja

AU - Schoen, Robert E.

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AU - Slattery, Martha L.

AU - White, Emily

AU - Hsu, Li

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