umu.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci
Show others and affiliations
2019 (English)In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578Article in journal (Refereed) Epub ahead of print
Abstract [en]

Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P < 5 × 10-8 in either analysis were taken forward for replication in up to 275,596 independent participants from UK Biobank. Lastly, a meta-analysis of the discovery and replication studies was performed. Sixteen SNVs were associated with at least one of the smoking behaviour traits (P < 5 × 10-8) in the discovery samples. Ten novel SNVs, including rs12616219 near TMEM182, were followed-up and five of them (rs462779 in REV3L, rs12780116 in CNNM2, rs1190736 in GPR101, rs11539157 in PJA1, and rs12616219 near TMEM182) replicated at a Bonferroni significance threshold (P < 4.5 × 10-3) with consistent direction of effect. A further 35 SNVs were associated with smoking behaviour traits in the discovery plus replication meta-analysis (up to 622,409 participants) including a rare SNV, rs150493199, in CCDC141 and two low-frequency SNVs in CEP350 and HDGFRP2. Functional follow-up implied that decreased expression of REV3L may lower the probability of smoking initiation. The novel loci will facilitate understanding the genetic aetiology of smoking behaviour and may lead to the identification of potential drug targets for smoking prevention and/or cessation.

Place, publisher, year, edition, pages
Nature Publishing Group, 2019.
National Category
Medical Genetics
Identifiers
URN: urn:nbn:se:umu:diva-156372DOI: 10.1038/s41380-018-0313-0PubMedID: 30617275OAI: oai:DiVA.org:umu-156372DiVA, id: diva2:1288340
Available from: 2019-02-13 Created: 2019-02-13 Last updated: 2019-02-27

Open Access in DiVA

fulltext(3117 kB)38 downloads
File information
File name FULLTEXT01.pdfFile size 3117 kBChecksum SHA-512
1128d95bceee73a4ccb68fa9ce8b220b4858ba2e5caeeb4102a5c46ad12ba2742826bc55f65a96eb94b1abb409f57def929de5e6fdf96ecc83cc4d535272da83
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Authority records BETA

Hallmans, GöranRenstrom, FridaRolandsson, OlovJansson, Jan-Håkan

Search in DiVA

By author/editor
Hallmans, GöranRenstrom, FridaRolandsson, OlovJansson, Jan-Håkan
By organisation
Nutritional ResearchDepartment of Biobank ResearchFamily MedicineDepartment of Public Health and Clinical Medicine
In the same journal
Molecular Psychiatry
Medical Genetics

Search outside of DiVA

GoogleGoogle Scholar
Total: 38 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 145 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf