Analysis of heritability and shared heritability based on genome-wide association studies for thirteen cancer types

Details

• Personal Author:
  Abnet CC ; Adami H-O ; Ahlbom A ; Albanes D ; Amary MF ; Amundadottir LT ; An S-J ; Andersson U ; Andriole G Jr. ; Andrulis IL ; Angelucci E ; Ansell SM ; Arici C ; Armstrong BK ; Arslan AA ; Austin MA ; Baris D ; Barkauskas DA ; Bassig BA ; Becker N ; Benavente Y ; Benhamou S ; Berg C ; Berndt SI ; Bernstein L ; Bertrand KA ; Birmann BM ; Black A ; Boeing H ; Boffetta P ; Boutron-Ruault M-C ; Bracci PM ; Brinton L ; Brooks-Wilson AR ; Bueno-de-Mesquita HB ; Burdett L ; Buring J ; Butler MA ; Cai Q ; Cancel-Tassin G ; Canzian F ; Carrato A ; Carreon T ; Carta A ; Chan JKC ; Chang ET ; Chang G-C ; Chang I-S ; Chang J ; Chang-Claude J ; Chen C ; Chen C-H ; Chen C-J ; Chen C-Y ; Chen H ; Chen K ; Chen K-C ; Chen K-Y ; Chen Y ; Chen Y-H ; Chen Y-M ; Chen Y-S ; Chien L-H ; Chirlaque M-D ; Choi JE ; De Vivo I ; Figueroa JD ; Lan Q ; Landi MT ; McGlynn KA ; Mirabello L ; Panagiotou O ; Purdue MP ; Rajaraman P ; Sampson JN ; Savage SA ; Taylor, Philip R. ; Van Den Berg D ; Wang Z ; Wheeler WA ; Yeager M
• Description:
  BACKGROUND: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. METHODS: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. RESULTS: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, hl (2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (P = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (P = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (P = 0.51, SE =0.18), and bladder and lung (P = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. CONCLUSION: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
  
  Additional Authors: Yoon H-I; Yu C-J; Yu H; Yu K; Yuan J-M; Zelenetz A; Zeleniuch-Jacquotte A; Zhang X-C; Zhang Y; Zhao X; Zhao Z; Zheng H; Zheng T; Zheng W; Zhou B; Zhu M; Zucca M; Boca SM; Cerhan JR; Ferri GM; Hartge P; Hsiung CA; Magnani C; Miligi L; Morton LM; Smedby KE; Teras LR; Vijai J; Wang SS; Brennan P; Caporaso NE; Hunter DJ; Kraft P; Rothman N; Silverman DT; Slager SL; Chanock SJ; Chatterjee N [Description provided by NIOSH]
  
  
• Subjects:
  Family Genetics Kidney Diseases Lung Lung Diseases Musculoskeletal Diseases Musculoskeletal System Neoplasms Occupational Health Race Factors Respiratory System Respiratory Tract Diseases Safety Smokers Tobacco Products Urogenital Diseases Urogenital System

  More +
• Keywords:
  Bladder-cancer Bladder-disease Bladder-disorders Bone-cancer Bone-disorders Cancer Cancer-rates Cigarette-smoking Families Genes Genetic-factors Kidney-disorders Kidney-tumors Lung-cancer Racial-factors Respiratory-system-disorders Statistical-analysis

  More +
• ISSN:
  0027-8874
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Ohio ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  DSHEFS - Division of Surveillance, Hazard Evaluations, and Field Studies
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  107
• Issue:
  12
• NIOSHTIC Number:
  nn:20047389
• Citation:
  J Natl Cancer Inst 2015 Dec; 107(12):djv279
• Contact Point Address:
  Joshua Sampson, PhD, Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, 7E594 Rockville, MD 20815
• Email:
  joshua.sampson@nih.gov
• Federal Fiscal Year:
  2016
• Peer Reviewed:
  True
• Source Full Name:
  Journal of the National Cancer Institute
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:3ba240329853eb2fe6175a5043c6e2bc73923b111d19eb5e645ace8c1e856c7512f62f50fd7c82651351759d76958d5bcc2bd927d9c62bebf9904ea180a9a198
• Download URL:
  https://stacks.cdc.gov/view/cdc/202466/cdc_202466_DS1.pdf
• File Type:
  [PDF - 1.29 MB ]