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Exploring rare and low-frequency variants in the Saguenay–Lac-Saint-Jean population identified genes associated with asthma and allergy traits

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...

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Autores principales: Morin, Andréanne, Madore, Anne-Marie, Kwan, Tony, Ban, Maria, Partanen, Jukka, Rönnblom, Lars, Syvänen, Ann-Christine, Sawcer, Stephen, Stunnenberg, Hendrik, Lathrop, Mark, Pastinen, Tomi, Laprise, Catherine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6303288/
https://www.ncbi.nlm.nih.gov/pubmed/30206357
http://dx.doi.org/10.1038/s41431-018-0266-4
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author Morin, Andréanne
Madore, Anne-Marie
Kwan, Tony
Ban, Maria
Partanen, Jukka
Rönnblom, Lars
Syvänen, Ann-Christine
Sawcer, Stephen
Stunnenberg, Hendrik
Lathrop, Mark
Pastinen, Tomi
Laprise, Catherine
author_facet Morin, Andréanne
Madore, Anne-Marie
Kwan, Tony
Ban, Maria
Partanen, Jukka
Rönnblom, Lars
Syvänen, Ann-Christine
Sawcer, Stephen
Stunnenberg, Hendrik
Lathrop, Mark
Pastinen, Tomi
Laprise, Catherine
author_sort Morin, Andréanne
collection PubMed
description 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 3ʹ-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.
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spelling pubmed-63032882018-12-24 Exploring rare and low-frequency variants in the Saguenay–Lac-Saint-Jean population identified genes associated with asthma and allergy traits Morin, Andréanne Madore, Anne-Marie Kwan, Tony Ban, Maria Partanen, Jukka Rönnblom, Lars Syvänen, Ann-Christine Sawcer, Stephen Stunnenberg, Hendrik Lathrop, Mark Pastinen, Tomi Laprise, Catherine Eur J Hum Genet Article 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 3ʹ-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. Springer International Publishing 2018-09-11 2019-01 /pmc/articles/PMC6303288/ /pubmed/30206357 http://dx.doi.org/10.1038/s41431-018-0266-4 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Morin, Andréanne
Madore, Anne-Marie
Kwan, Tony
Ban, Maria
Partanen, Jukka
Rönnblom, Lars
Syvänen, Ann-Christine
Sawcer, Stephen
Stunnenberg, Hendrik
Lathrop, Mark
Pastinen, Tomi
Laprise, Catherine
Exploring rare and low-frequency variants in the Saguenay–Lac-Saint-Jean population identified genes associated with asthma and allergy traits
title Exploring rare and low-frequency variants in the Saguenay–Lac-Saint-Jean population identified genes associated with asthma and allergy traits
title_full Exploring rare and low-frequency variants in the Saguenay–Lac-Saint-Jean population identified genes associated with asthma and allergy traits
title_fullStr Exploring rare and low-frequency variants in the Saguenay–Lac-Saint-Jean population identified genes associated with asthma and allergy traits
title_full_unstemmed Exploring rare and low-frequency variants in the Saguenay–Lac-Saint-Jean population identified genes associated with asthma and allergy traits
title_short Exploring rare and low-frequency variants in the Saguenay–Lac-Saint-Jean population identified genes associated with asthma and allergy traits
title_sort exploring rare and low-frequency variants in the saguenay–lac-saint-jean population identified genes associated with asthma and allergy traits
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6303288/
https://www.ncbi.nlm.nih.gov/pubmed/30206357
http://dx.doi.org/10.1038/s41431-018-0266-4
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