Shared heritability and functional enrichment across six solid cancers

• Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (rg = 0.57, p = 4.6 × 10−8), breast and ovarian cancer (rg = 0.24, p = 7 × 10−5), breast and lung cancer (rg = 0.18, p =1.5 × 10−6) and breast and colorectal cancer (rg = 0.15, p = 1.1 × 10−4). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis. © 2019, The Author(s).

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska grundvetenskaper -- Medicinsk genetik (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Reproduktionsmedicin och gynekologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Obstetrics, Gynecology and Reproductive Medicine (hsv//eng)

Nyckelord

genome-wide association

susceptibility loci

breast-cancer

risk-factors

lung-cancer

partitioning heritability

mendelian

randomization

genetic architecture

analyses identify

cell-types

IBELL

Catalan Inst Oncol

Barcelona 08908

Spain.

[Moreno

Victor] Univ Barcelona

Barcelona 08908

Spain.

[Moysich

Kirsten B.] Roswell Pk Canc Inst

Div Canc Prevent & Control

Elm & Carlton St

Buffalo

NY

[Muir

Kenneth] Univ Manchester

Div Populat Hlth Hlth Serv Res & Primary Care

Oxford Rd

[Muir

Kenneth] Univ Warwick

Warwick Med Sch

Div Hlth Sci

Coventry CV4 7AL

W Midlands

[Mulligan

Anna Marie] Univ Toronto

Dept Lab Med & Pathobiol

1 Kings Coll Circle

Toronto

ON M5S

[Mulligan

Anna Marie] Univ Hlth Network

Lab Med Program

200 Elizabeth St

Toronto

ON M5G 2C4

[Nathanson

Katherine L.] Univ Penn

Perelman Sch Med

Abramson Canc Ctr

Dept Med

3400 Civ Ctr

[Neal

David E.] Univ Cambridge

Addenbrookes Hosp

Dept Oncol

Cambridge CB1 8RN

England.

[Ness

Andrew R.] Univ Bristol

NIHR Bristol Biomed Res Ctr Nutr Theme

Upper Maudlin St

Bristol BS2

[Neuhausen

Susan L.] Beckman Res Inst City Hope

Dept Populat Sci

1500 E Duarte

Duarte

CA 91010

[Nevanlinna

Heli] Univ Helsinki

Helsinki Univ Hosp

Dept Obstet & Gynecol

Haartmaninkatu 8

FIN-

[Newcomb

Lisa F.] Univ Washington

Dept Urol

Seattle

WA 98195 USA.

[Nielsen

Finn Cilius] Copenhagen Univ Hosp

Ctr Genom Med

Rigshosp

Blegdamsvej 9

DK-2100

[Nikitina-Zake

Liene] Latvian Biomed Res & Study Ctr

Ratsupites Str 1

LV-1067 Riga

Latvia.

[Nussbaum

Robert L.] Univ Calif San Francisco

Canc Genet & Prevent Program

1600 Div St

San

[Offit

Kenneth] Mem Sloan Kettering Canc Ctr

Dept Canc Biol & Genet

Clin Genet Res Lab

1275 York

[Offit

Kenneth] Mem Sloan Kettering Canc Ctr

Dept Med

Clin Genet Serv

1275 York Ave

New York

97239 USA.

[Peters

Wilbert H. M.] Radboud Univ Nijmegen

Med Ctr

Dept Gastroenterol

Geert Grooteplein Zuid

[Phipps

Amanda I.

Stanford

Janet L.

Peters

Ulrike

Lindstrom

Sara] Univ Washington

Sch Publ Hlth

[Plaseska-Karanfilska

Dijana] Macedonian Acad Sci & Arts

Res Ctr Genet Engn & Biotechnol Georgi

fremov

Blvd Krste Petkov Misirkov

Skopje 1000

Macedonia.

[Pring

Miranda] Univ Bristol

Bristol Dent Sch

Lower Maudlin St

Bristol BS1 2LY

Avon

England.

[Radice

Paolo] INT

Fdn IRCCS

Dept Res

Unit Mol Bases Genet Risk & Genet Testing

Via Giacomo

[Stefansson

Kari] Decode Genet

Sturlugata 8

IS-101 Reykjavik

Iceland.

[Ramus

Susan J.] Univ NSW Sydney

Sch Womens & Childrens Hlth

Fac Med

18 High St

Sydney

NSW

[Ramus

Susan J.] Garvan Inst Med Res

Kinghorn Canc Ctr

384 Victoria St

Sydney

NSW 2010

[Raskin

Leon

Zheng

Wei] Vanderbilt Univ

Sch Med

Vanderbilt Ingram Canc Ctr

Div Epidemiol

Dept

[Rennert

Gad

Rennert

Hedy S.] Carmel Hosp

Clalit Natl Canc Control Ctr

7 Michal St

IL-34362 Haifa

[Rennert

Gad

Rennert

Hedy S.] Technion Fac Med

7 Michal St

IL-34362 Haifa

Israel.

[van Rensburg

Elizabeth J.] Univ Pretoria

Dept Genet

Private Bag X323

ZA-0007 Arcadia

South

[Risch

Harvey A.] Yale Sch Publ Hlth

Dept Chron Dis Epidemiol

60 Coll St

New Haven

CT 06510 USA.

[Risch

Angela] Salzburg Univ

Dept Mol Biol

Canc Ctr Cluster Salzburg

PLUS

Billrothstr11

A-5020

[Risch

Angela] DKFZ German Canc Res Ctr

Div Epigen & Canc Risk Factors

Neuenheimer Feld 280

D-

[Risch

Angela] German Ctr Lung Res DZL

TLRC H

D-69120 Heidelberg

Germany.

[Roobol

Monique J.] Erasmus Univ

Med Ctr

Dept Urol

Wytemaweg 80

NL-3015 CN Rotterdam

[Rosenstein

Barry S.] Icahn Sch Med Mt Sinai

Dept Radiat Oncol

1425 Madison Ave

New York

NY

[Rosenstein

Barry S.] Icahn Sch Med Mt Sinai

Dept Genet & Genom Sci

1425 Madison Ave

New York

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