Table 3.
Summery of published genome-wide association study in respiratory diseases and traits
| Gene | Phenotype | Sample size and ethnicity | Year | Genome-wide significant findings (Yes/No) | Comments | Ref |
|---|---|---|---|---|---|---|
| ORMDL3 | Childhood asthma | Discovery:994 /1,243 * (Caucasians)Replication:2320 subjects from Germany (Caucasians)3301 subjects from the British 1958 Birth Cohort (Caucasians) | 2007 | Yes | SNPs in the 17q21 region showed a strong association with childhood asthma in both a UK family cohort and German case-control samples. SNPs in this region were also associated with increased ORMDL3 mRNA expression in lymphoblastoid cell lines from asthmatic children. | (Moffatt, Kabesch et al., 2007) |
| GSTO2 IL6R | Quantitative pulmonary function measures | 1097–1222 (depending on phenotype) individuals from the Framingham Heart Study population. (Caucasians) | 2007 | No | The study utilized data on 71 000 SNPs. Two genes where proposed as potential candidate genes: GSTO2 and IL6R. | (Wilk, Walter et al., 2007) |
| CHI3L1 | Asthma, bronchial hyperresponsiveness and measures of pulmonary function | 632 Hutterites(Caucasian) | 2008 | Yes | Variants associated with elevated serum YKL-40 levels. YKL-40 was previously reported to be increased in the lungs and circulation of patients with severe asthma. | (Ober, Tan et al., 2008) |
| PDE4D | Asthma | Discovery:359 /846 * (Caucasians)Replication:Ten independent populations with different ethnicities totalling 18 891 individuals (4342 cases) | 2009 | No | Cases from the Childhood Asthma Management Program (CAMP) and genetically matched controls from the Illumina ICONdb public resource. The strongest region of association seen was on chromosome 5q12 in PDE4D | (Himes, Hunninghake et al., 2009) |
| ADRA1B PRNP DPP10 | Asthma | Discovery:464 /471 * (African American)929 asthmatics and their family members (African Caribbean)Replication:994 / 1243* and 207 families (Caucasians)1456/1973*, 200/200*, 264 /186*, 208/179 * (African Americans) | 2009 | No | None of the SNPs implicated in the discovery population were replicated in two European cohorts and four additional case-control studies of African Americans. | (Mathias, Grant et al., 2010) |
| TLE4 CHCHD9 | Childhood asthma | Discovery:492 Trios (Mexicans)Replication:177 Trios (Mexicans) | 2009 | No | Cases were children with asthma, predominantly atopic by skin prick test, and their parents using the Illumina HumanHap 550 K BeadChip. | (Hancock, Romieu et al., 2009) |
| IL1RL1 IKZF2 GATA2 IL5 SH2B3 | Plasma eosinophil count | Discovery:9392 (Icelanders)Replication:12 118 (Europeans)5212 (East Asians) | 2009 | Yes | Variants in IL1RL1, IKZF2, GATA2, IL5, and SH2B3 showed association with eosinophil count. Three SNPs in IL1RL1, IL33 and WDR36 have also showed association with atopic asthma, with the IL1RL1 SNP showing association with asthma as well. | (Gudbjartsson, Bjornsdottir et al., 2009) |
| DENND1B CRB1 | Asthma | Discovery:793/1988* (Europeans)Replication:917/1546* (Europeans)1667/2045* (African Americans) | 2010 | Yes | The study also implicated the 17q21 locus harbouring ORMDL3 | (Sleiman, Flory et al., 2010) |
| RAD50 IL13 HLA-DQB1 | Asthma | 473/1892* (Caucasians) | 2010 | No | Cases from The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) and 1892 Illumina general population controls. | (Li, Howard et al., 2010) |
| HHIP | FEV1/FVC ratio | Discovery:7691 (Caucasians)Replication:835 (Caucasians) | 2009 | Yes | Individuals from the Framingham Heart Study. This time, by genotyping more SNPs (550 000 SNPs) in more individuals (7691), the study identified associations of SNPs on chromosome 4q31 near HHIP with the percent predicted FEV1/FVC ratio | (Wilk, Chen et al., 2009) |
| CHRNA 3 CHRNA 5 HHIP | COPD | Discovery:823/810* (Caucasians)Replication:389/472* (Caucasians)2840 Caucasians family members | 2009 | Yes | The first GWAS for COPD. The study investigated association with ∼500 000 SNPs. The HHIP locus did not reach genome-wide significance. | (Pillai, Ge et al., 2009) |
| GSTCD TNS1 HHIP HTR4 AGER THSD4 | Lung function measures(FEV1 and FEV1/FVC) | Discovery:20 288 (Caucasians)Replication:32 184 direct genotyping (Caucasians)22 092 in silico replication (Caucasians)54 276 total | 2010 | Yes | SpiroMeta consortium meta-analysis.>2.5 million genotyped and imputed SNPs tested.mRNA expression analysis showed all variants to be expressed in lung tissue. | (Repapi, Sayers et al., 2010) |
| GSTCD HHIP HTR4 AGER GPR126 ADAM19 FAM13A PTCH1 PID1 | Lung function measures(FEV1 and FEV1/FVC) | Discovery:20 890 (Caucasians)Replication:16 178 in silico (Caucasians) | 2010 | Yes | CHARGE consortium meta-analysis. | (Hancock, Eijgelsheim et al., 2010) |
| FAM13A HHIP CHRNA3 CHRNA5 IREB2 | COPD | Discovery:2940 /1380* (Caucasians)Replication:502/504* and two family-basedcohorts (n = 3808) (Caucasians) | 2010 | Yes | (Cho, Boutaoui et al., 2010) | |
| HLA-DQ IL1RL1 IL18R1 IL33 SMAD3 IL2RB GSDMA GSDMB | Asthma | Discovery:10 365/16 110 * (Caucasians) | 2010 | Yes | The GABRIEL (A Multidisciplinary Study to Identify the Genetic and Environmental Causes of Asthma in the European Community) Consortium.Association with the ORMDL3/GSDMB locus on chromosome 17q21 was specific to childhood-onset disease. Only HLA-DR showed a significant genome wide association with the total serum IgE concentration | (Moffatt, Gut et al., 2010) |
| BICD1 | Emphysema (Both qualitative and quantitative) | Caucasian subjects from three cohorts (n = 1586, 435 and 362) | 2010 | Yes | BICD1 gene were previously associated with telomere length in leukocytes | (Kong, Cho et al., 2010) |
*
Number of cases/number of controls.