Estimating the heritability of colorectal cancer

被引：107

作者：

Jiao, Shuo ^{[1
]}

Peters, Ulrike ^{[1
]}

Berndt, Sonja ^{[2
]}

Brenner, Hermann ^{[15
]}

Butterbach, Katja ^{[15
]}

Caan, Bette J. ^{[3
]}

Carlson, Christopher S. ^{[1
,8
,9
]}

Chan, Andrew T. ^{[4
,5
]}

Chang-Claude, Jenny ^{[6
]}

Chanock, Stephen ^{[2
]}

Curtis, Keith R. ^{[1
]}

Duggan, David ^{[7
]}

Gong, Jian ^{[1
]}

Harrison, Tabitha A. ^{[1
]}

Hayes, Richard B. ^{[9
,10
]}

Henderson, Brian E. ^{[11
]}

Hoffmeister, Michael ^{[15
]}

Kolonel, Laurence N. ^{[12
]}

Le Marchand, Loic ^{[13
]}

Potter, John D. ^{[1
,8
,9
,14
]}

Rudolph, Anja ^{[3
]}

Schoen, Robert E. ^{[15
]}

Seminara, Daniela ^{[3
]}

Slattery, Martha L. ^{[16
]}

White, Emily ^{[1
]}

Hsu, Li ^{[1
]}

机构：

[1] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA

[2] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA

[3] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA

[4] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany

[5] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany

[6] Kaiser Permanente Med Care Program, Div Res, Oakland, CA 94611 USA

[7] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA

[8] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA

[9] Harvard Univ, Sch Med, Boston, MA USA

[10] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA

[11] Translat Genom Res Inst, Phoenix, AZ USA

[12] NYU, Sch Med, Div Epidemiol, New York, NY USA

[13] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96822 USA

[14] Massey Univ, Ctr Publ Hlth Res, Wellington, New Zealand

[15] Univ Pittsburgh, Med Ctr, Dept Med & Epidemiol, Pittsburgh, PA USA

[16] Univ Utah, Hlth Sci Ctr, Dept Internal Med, Salt Lake City, UT USA

来源：

HUMAN MOLECULAR GENETICS | 2014年 / 23卷 / 14期

基金：

美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; COLON-CANCER; COMMON SNPS; RISK LOCI; HEALTH; VARIANTS; PROSTATE; DISEASE; DESIGN;

D O I：

10.1093/hmg/ddu087

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 in GWAS was 0.65% (95% CI:0.3-1%; P = 1.11 x 10-16), whereas the heritability explained by all common SNPs was at least 7.42% (95% CI: 4.71-10.12%; P = 8.13 x 10(-8)), suggesting that many 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 x smoking interaction explained a significant proportion of the CRC variance (P = 1.26 x 10(-2)). In summary, our results suggest that known CRC SNPs only explain a small proportion of the heritability and more common SNPs have yet to be identified.

引用

页码：3898 / 3905

页数：8

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