TY - JOUR
T1 - Exploring rare and low-frequency variants in the Saguenay–Lac-Saint-Jean population identified genes associated with asthma and allergy traits
AU - Morin, Andréanne
AU - Madore, Anne Marie
AU - Kwan, Tony
AU - Ban, Maria
AU - Partanen, Jukka
AU - Rönnblom, Lars
AU - Syvänen, Ann Christine
AU - Sawcer, Stephen
AU - Stunnenberg, Hendrik
AU - Lathrop, Mark
AU - Pastinen, Tomi
AU - Laprise, Catherine
N1 - Publisher Copyright:
© 2018, The Author(s).
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85053410071&partnerID=8YFLogxK
U2 - 10.1038/s41431-018-0266-4
DO - 10.1038/s41431-018-0266-4
M3 - Article
C2 - 30206357
AN - SCOPUS:85053410071
SN - 1018-4813
VL - 27
SP - 90
EP - 101
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 1
ER -