Exploring rare and low-frequency variants in the Saguenay-Lac-Saint-Jean population identified genes associated with asthma and allergy traits.
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Authors
Morin, Andréanne
Madore, Anne-Marie
Kwan, Tony
Ban, Maria
Partanen, Jukka
Rönnblom, Lars
Syvänen, Ann-Christine
Stunnenberg, Hendrik
Lathrop, Mark
Pastinen, Tomi
Laprise, Catherine
Publication Date
2019-01Journal Title
Eur J Hum Genet
ISSN
1018-4813
Publisher
Springer Science and Business Media LLC
Volume
27
Issue
1
Pages
90-101
Language
eng
Type
Article
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Morin, A., Madore, A., Kwan, T., Ban, M., Partanen, J., Rönnblom, L., Syvänen, A., et al. (2019). Exploring rare and low-frequency variants in the Saguenay-Lac-Saint-Jean population identified genes associated with asthma and allergy traits.. Eur J Hum Genet, 27 (1), 90-101. https://doi.org/10.1038/s41431-018-0266-4
Abstract
The Saguenay-Lac-Saint-Jean (SLSJ) region is located in northeastern Quebec and is known for its unique demographic history and founder effect. As founder populations are enriched with population-specific variants, we characterized the variants distribution in SLSJ and compared it with four European populations (Finnish, Sweden, United Kingdom and France), of which the Finnish population is another founder population. Targeted sequencing of the coding and non-coding immune regulatory regions of the SLSJ asthma familial cohort and the four European populations were performed. Rare and low-frequency coding and non-coding regulatory variants identified in the SLSJ population were then investigated for variant- and gene-level associations with asthma and allergy-related traits (eosinophil percentage, immunoglobulin (Ig) E levels and lung function). Our data showed that (1) rare or deleterious variants were not enriched in the two founder populations as compared with the three non-founder European populations; (2) a larger proportion of founder population-specific variants occurred with higher frequencies; and (3) low-frequency variants appeared to be more deleterious. Furthermore, a rare variant, rs1386931, located in the 3'-UTR of CXCR6 and intron of FYCO1 was found to be associated with eosinophil percentage. Gene-based analyses identified NRP2, MRPL44 and SERPINE2 to be associated with various asthma and allergy-related traits. Our study demonstrated the usefulness of using a founder population to identify new genes associated with asthma and allergy-related traits; thus better understand the genes and pathways implicated in pathophysiology.
Keywords
Humans, Asthma, Microtubule-Associated Proteins, DNA-Binding Proteins, Neuropilin-2, Mitochondrial Proteins, Ribosomal Proteins, Transcription Factors, Gene Frequency, Polymorphism, Single Nucleotide, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, Child, Child, Preschool, Quebec, Female, Male, Serpin E2, Receptors, CXCR6
Identifiers
External DOI: https://doi.org/10.1038/s41431-018-0266-4
This record's URL: https://www.repository.cam.ac.uk/handle/1810/283109
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