Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
31608842
TITLE
and Asthma on the Island of Tristan da Cunha.
ABSTRACT
A high prevalence of asthma has been documented among the inhabitants of Tristan da Cunha, an isolated island in the South Atlantic. The population derives from just 28 founders. We performed lung function testing, including methacholine inhalation challenge, allergen skin prick testing, and collected DNA from essentially all of the current island population (269 individuals), and genotyped a panel of 43 single-nucleotide polymorphisms (SNPs) reported as associated with asthma and atopy. We carried out a mixed-model association analysis using the known pedigree. There were 96 individuals diagnosed as asthmatic (36%), and heritability estimates were similar to those from nonisolated population samples (multifactorial threshold model, h2 = 48%). The first component from a genetic principal components analysis using the entire SNP panel was nonlinearly associated with asthma, with the maximum risk to those intermediate to reference (Human Genome Diversity Project) European and African samples means. The single most strongly associated SNP was rs2786098 (p = 5.5 × 10-5), known to regulate the gene DENND1B. This explained approximately one-third of the trait heritability, with an allelic odds ratio for the A allele of 2.6. Among A/A carriers, 10 out of 12 individuals were asthmatic. The rs2786098*A variant was initially reported to decrease the risk of childhood (atopic) asthma in European but slightly increase the risk in African-descended populations, and does significantly alter Th2 cell function. Despite an absence of overall association with this variant in recent asthma genome wide association studies meta-analyses, an effect may exist on the particular genetic background of the Tristan da Cunha population.
DATE PUBLISHED
2019 Oct 14
HISTORY
PUBSTATUS PUBSTATUSDATE
entrez 2019/10/15 06:00
pubmed 2019/10/15 06:00
medline 2019/10/15 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Duffy DL Duffy David L DL Department of Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Siminovitch KA Siminovitch Katherine A KA Departments of Medicine and Immunology, University of Toronto, Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital and Toronto General Research Institute, University Health Network, Toronto, ON, Canada.
Zamel R Zamel Ricardo R Division of Thoracic Surgery, Toronto General Hospital, University Health Network, University of Toronto, Toronto, ON, Canada.
Chapman KR Chapman Kenneth R KR University of Toronto Asthma and Airway Centre, University Health Network, Toronto, ON, Canada.
Martin NG Martin Nicholas G NG Department of Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Zamel N Zamel Noe N University of Toronto Asthma and Airway Centre, University Health Network, Toronto, ON, Canada.
INVESTIGATORS
JOURNAL
VOLUME:
ISSUE:
TITLE: Twin research and human genetics : the official journal of the International Society for Twin Studies
ISOABBREVIATION: Twin Res Hum Genet
YEAR: 2019
MONTH: Oct
DAY: 14
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1832-4274
ISSNTYPE: Print
MEDLINE JOURNAL
MEDLINETA: Twin Res Hum Genet
COUNTRY: England
ISSNLINKING: 1832-4274
NLMUNIQUEID: 101244624
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
COMMENTS AND CORRECTIONS
GRANTS
GENERAL NOTE
KEYWORDS
KEYWORD
Asthma
genetics association
MESH HEADINGS
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
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