Genome-wide association study of lung function and clinical implication in heavy smokers

BMC Medical Genetics

Table 5 Joint analysis of 10 SNPs with emphysema, clinical symptoms, and exacerbation

Genetic Score^a	8–11 (n = 228)	12–13 (n = 643)	14–15 (n = 612)	16–18 (n = 149)	P valueǂ
CT Evidence of Emphysema (TLC % Area < − 950 HU^b)	5.54 ± 6.59	7.60 ± 9.84	8.67 ± 10.4	12.5 ± 12.4	< 0.0001
CT Evidence of Airtrapping (RV % Area < − 856 HU^b)	21.8 ± 18.1	24.0 ± 20.6	27.6 ± 21.0	33.9 ± 23.2	< 0.0001
BODE Index	1.15 ± 1.62	1.33 ± 1.75	1.61 ± 1.98	2.21 ± 2.41	< 0.0001
COPD Assessment Test (CAT)	12.7 ± 8.0	13.0 ± 8.0	14.0 ± 8.2	13.5 ± 7.9	0.07
St. George’s Respiratory Questionnaire (SGRQ) Total Score	30.4 ± 19.7	30.3 ± 19.6	32.9 ± 20.0	35.5 ± 20.6	0.0044
6-Minute Walk Distance (6MWD, meters)	416 ± 114	415 ± 111	418 ± 124	390 ± 126	0.0086
Exacerbations requiring ED Visit or Hospitalization in last 12 months (% Yes)	7.5%	6.5%	11%	14%	0.001

^aGenetic scores (the number of risk alleles) of 10 candidate SNPs (rs28929474 in SERPINA1, rs1980057 in HHIP, rs2869967 in FAM13A1, rs2070600 in AGER, rs1435867 in PID1, rs12477314 in HDAC4, rs1529672 in RARB, rs12914385 in CHRNA3, rs10498635 in RIN3, and rs615098 in MMP12). 1632 SPIROMICS non-Hispanic White smokers (GOLD stage 0–4) were included. Eight subjects with TT genotype of rs28929474 in SERPINA1 (PiZZ genotype) were excluded. ^b CT scan-based measures of emphysema (− 950 Hounsfield Units or less [%Bilateral Lung Area ≤ − 950]) and airtrapping (− 856 Hounsfield Units or less [%Bilateral Lung Area ≤ − 856]) measures log-transformed for analysis and adjusted by study site, age, sex, height, BMI, and pack-year smoking history. ǂGeneralized linear model was used with adjusted of age, sex, current smoking status, and pack-years of cigarette smoking. In generalized linear models, CT evidence of emphysema and airtrapping were natural logarithm transformed; 6MWD was logarithm (base 10) transformed

ISSN: 1471-2350