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Family-Based Association Study of Pulmonary Function in a Population in Northeast Asia.

Son HY, Sohn SW, Im SH, Kim HJ, Lee MK, Gombojav B, Kwon HS, Park DS, Kim HL, Min KU, Sung J, Seo JS, Kim JI - PLoS ONE (2015)

Bottom Line: Genome-wide linkage and association studies have identified a number of genes and genetic loci associated with pulmonary function.We also found two adjacent candidate genes (UNC93A and TTLL2) in the 6q27 region, which has been previously identified as a pulmonary function locus in the Framingham cohort study.Our findings suggest that novel candidate genes (TMEM132C, UNC93A and TTLL2) in two different regions are associated with pulmonary function in a population in northeast Asia.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, Republic of Korea.

ABSTRACT
The spirometric measurement of pulmonary function by measuring the forced expiratory volume in one second (FEV1) is a heritable trait that reflects the physiological condition of the lung and airways. Genome-wide linkage and association studies have identified a number of genes and genetic loci associated with pulmonary function. However, limited numbers of studies have been reported for Asian populations. In this study, we aimed to investigate genetic evidence of pulmonary function in a population in northeast Asia. We conducted a family-based association test with 706 GENDISCAN study participants from 72 Mongolian families to determine candidate genetic determinants of pulmonary function. For the replication, we chose seven candidate single nucleotide polymorphisms (SNPs) from the 5 loci, and tested 1062 SNPs for association with FEV1 from 2,729 subjects of the Korea Healthy Twin study. We identified TMEM132C as a potential candidate gene at 12q24.3, which is a previously reported locus of asthma and spirometric indices. We also found two adjacent candidate genes (UNC93A and TTLL2) in the 6q27 region, which has been previously identified as a pulmonary function locus in the Framingham cohort study. Our findings suggest that novel candidate genes (TMEM132C, UNC93A and TTLL2) in two different regions are associated with pulmonary function in a population in northeast Asia.

No MeSH data available.


Related in: MedlinePlus

Regional plots for discovery and replication loci associated with FEV1.The purple diamonds indicate the most significant SNP of each region, and nearby SNPs are color coded according to the level of LD with the top SNP. The x-axis shows chromosomal position. The left y axis shows the significance of the association, and the right y-axis shows a recombination rate across the region. Estimated recombination rates from the 1000 Genome (JPT+CHB, hg18) database are plotted with the blue line to reflect the local LD structure. Discovery (a) and replication (b) result of the TMEM132C region on 12q24.3. Discovery (c) and replication (d) result of the UNC93A and TTLL2 region on 6q27. The regional plots were created using LocusZoom.
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pone.0139716.g002: Regional plots for discovery and replication loci associated with FEV1.The purple diamonds indicate the most significant SNP of each region, and nearby SNPs are color coded according to the level of LD with the top SNP. The x-axis shows chromosomal position. The left y axis shows the significance of the association, and the right y-axis shows a recombination rate across the region. Estimated recombination rates from the 1000 Genome (JPT+CHB, hg18) database are plotted with the blue line to reflect the local LD structure. Discovery (a) and replication (b) result of the TMEM132C region on 12q24.3. Discovery (c) and replication (d) result of the UNC93A and TTLL2 region on 6q27. The regional plots were created using LocusZoom.

Mentions: The results of the family-based association between the genome-wide SNPs and FEV1 are shown in a Manhattan plot (Fig 1). Each of the approximately 510,000 SNPs is represented by single dot. Five regions were identified that contained seven suggestively associated SNPs with P values less than 1 × 10−5 (Table 2). The most significant association was observed in the intronic region of TMEM132C (rs12582875, P = 2.17 × 10−6) at 12q24.3 (Fig 2a). On chromosome 6q27, two SNPs (rs4710230 and rs3010558, P = 2.77 × 10−6 and P = 8.99 × 10−6, respectively) were located 21.7 Kb and 7.8 Kb upstream of UNC93A (Fig 2c). On chromosome 3p14.1, rs264676 (P = 3.28 × 10−6) was located in the MAGI1 intron. We found one SNP (rs7504607) at 18q23, was associated with FEV1 phenotype, but has no candidate gene within 200 kb. At chromosome 4q27, rs6855113 and rs6831851 (both P = 9.48 × 10−6) were located 17kb and 33 kb upstream of the MAD2L1 gene, respectively.


Family-Based Association Study of Pulmonary Function in a Population in Northeast Asia.

Son HY, Sohn SW, Im SH, Kim HJ, Lee MK, Gombojav B, Kwon HS, Park DS, Kim HL, Min KU, Sung J, Seo JS, Kim JI - PLoS ONE (2015)

Regional plots for discovery and replication loci associated with FEV1.The purple diamonds indicate the most significant SNP of each region, and nearby SNPs are color coded according to the level of LD with the top SNP. The x-axis shows chromosomal position. The left y axis shows the significance of the association, and the right y-axis shows a recombination rate across the region. Estimated recombination rates from the 1000 Genome (JPT+CHB, hg18) database are plotted with the blue line to reflect the local LD structure. Discovery (a) and replication (b) result of the TMEM132C region on 12q24.3. Discovery (c) and replication (d) result of the UNC93A and TTLL2 region on 6q27. The regional plots were created using LocusZoom.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4592257&req=5

pone.0139716.g002: Regional plots for discovery and replication loci associated with FEV1.The purple diamonds indicate the most significant SNP of each region, and nearby SNPs are color coded according to the level of LD with the top SNP. The x-axis shows chromosomal position. The left y axis shows the significance of the association, and the right y-axis shows a recombination rate across the region. Estimated recombination rates from the 1000 Genome (JPT+CHB, hg18) database are plotted with the blue line to reflect the local LD structure. Discovery (a) and replication (b) result of the TMEM132C region on 12q24.3. Discovery (c) and replication (d) result of the UNC93A and TTLL2 region on 6q27. The regional plots were created using LocusZoom.
Mentions: The results of the family-based association between the genome-wide SNPs and FEV1 are shown in a Manhattan plot (Fig 1). Each of the approximately 510,000 SNPs is represented by single dot. Five regions were identified that contained seven suggestively associated SNPs with P values less than 1 × 10−5 (Table 2). The most significant association was observed in the intronic region of TMEM132C (rs12582875, P = 2.17 × 10−6) at 12q24.3 (Fig 2a). On chromosome 6q27, two SNPs (rs4710230 and rs3010558, P = 2.77 × 10−6 and P = 8.99 × 10−6, respectively) were located 21.7 Kb and 7.8 Kb upstream of UNC93A (Fig 2c). On chromosome 3p14.1, rs264676 (P = 3.28 × 10−6) was located in the MAGI1 intron. We found one SNP (rs7504607) at 18q23, was associated with FEV1 phenotype, but has no candidate gene within 200 kb. At chromosome 4q27, rs6855113 and rs6831851 (both P = 9.48 × 10−6) were located 17kb and 33 kb upstream of the MAD2L1 gene, respectively.

Bottom Line: Genome-wide linkage and association studies have identified a number of genes and genetic loci associated with pulmonary function.We also found two adjacent candidate genes (UNC93A and TTLL2) in the 6q27 region, which has been previously identified as a pulmonary function locus in the Framingham cohort study.Our findings suggest that novel candidate genes (TMEM132C, UNC93A and TTLL2) in two different regions are associated with pulmonary function in a population in northeast Asia.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, Republic of Korea.

ABSTRACT
The spirometric measurement of pulmonary function by measuring the forced expiratory volume in one second (FEV1) is a heritable trait that reflects the physiological condition of the lung and airways. Genome-wide linkage and association studies have identified a number of genes and genetic loci associated with pulmonary function. However, limited numbers of studies have been reported for Asian populations. In this study, we aimed to investigate genetic evidence of pulmonary function in a population in northeast Asia. We conducted a family-based association test with 706 GENDISCAN study participants from 72 Mongolian families to determine candidate genetic determinants of pulmonary function. For the replication, we chose seven candidate single nucleotide polymorphisms (SNPs) from the 5 loci, and tested 1062 SNPs for association with FEV1 from 2,729 subjects of the Korea Healthy Twin study. We identified TMEM132C as a potential candidate gene at 12q24.3, which is a previously reported locus of asthma and spirometric indices. We also found two adjacent candidate genes (UNC93A and TTLL2) in the 6q27 region, which has been previously identified as a pulmonary function locus in the Framingham cohort study. Our findings suggest that novel candidate genes (TMEM132C, UNC93A and TTLL2) in two different regions are associated with pulmonary function in a population in northeast Asia.

No MeSH data available.


Related in: MedlinePlus