Table 2.

Novel genome-wide significant signals of association with extremes of forced expiratory volume in 1 s or smoking behaviour

		Locus	Non-coded/coded allele (minor allele)	Imputation info score*	Smoking status	MAF (MAC)†	OR (95% CI)	p value (genomic control corrected)	Association with COPD‡		Effect on FEV1
									OR (95% CI)	p value	Beta (SE)§	p value
Extremes of FEV1: low vs high FEV1
Genome-wide significant in heavy smokers
	Chr12:114743533	RBM19/TBX5	T/C (T)	0·737	Never	0·002 (60)	0·97 (0·57–1·67)	0·90	1·16 (0·54–2·51)	0·71	0·101 (0·118)	0·39
	..	..	..	..	Heavy	0·001 (39)	11·73 (5·03–27·32)	1·16 × 10−8	6·44 (2·89–14·37)	5·40 × 10−6	−0·728 (0·151)	1·31 × 10−6
Genome-wide significant in never smokers
	rs34712979 ¶‖, Chr4:106819053	NPNT	G/A (A)	1·000	Never	0·268 (7842)	1·27 (1·20–1·34)	9·62 × 10−16	1·36 (1·27–1·46)	2·10 × 10−18	−0·087 (0·010)	2·27 × 10−17
	..	..	..	..	Heavy	0·261 (7636)	1·18 (1·11–1·25)	1·10 × 10−8	1·26 (1·18–1·34)	5·43 × 10−13	−0·056 (0·010)	4·22 × 10−8
	rs9274600¶, Chr6:32635592	HLA-DQB1/HLA-DQA2	A/G (G)	0·962	Never	0·472 (13 838)	1·18 (1·13–1·25)	1·26 × 10−10	1·24 (1·16–1·32)	1·95 × 10−11	−0·057 (0·009)	6·72 × 10−10
	..	..	..	..	Heavy	0·468 (13 719)	1·05 (1·00–1·10)	0·096	1·08 (1·02–1·14)	8·58 × 10−3	−0·019 (0·009)	0·037
	rs2532349, Chr17:44339473	KANSL1	A/G (G)	0·976	Never	0·242 (7088)	1·22 (1·15–1·29)	1·66 × 10−10	1·24 (1·16–1·34)	3·97 × 10−9	−0·063 (0·011)	3·22 × 10−9
	..	..	..	..	Heavy	0·233 (6832)	1·15 (1·08–1·21)	1·47 × 10−5	1·14 (1·07–1·22)	9·56 × 10−5	−0·050 (0·011)	3·64 × 10−6
	rs7218675, Chr17:73513185	TSEN54	C/A (C)	0·997	Never	0·291 (8538)	1·18 (1·11–1·25)	1·18 × 10−8	1·22 (1·14–1·31)	4·56 × 10−9	−0·052 (0·010)	1·94 × 10−7
	..	..	..	..	Heavy	0·290 (8503)	1·04 (0·98–1·09)	0·23	1·06 (1·00–1·13)	0·059	−0·017 (0·010)	0·080
	rs2047409, Chr4:106137033	TET2	G/A (G)	0·998	Never	0·345 (10 117)	1·17 (1·11–1·23)	1·31 × 10−8	1·17 (1·10–1·25)	1·64 × 10−6	−0·056 (0·009)	4·19 × 10−9
	..	..	..	..	Heavy	0·356 (10 440)	1·07 (1·02–1·13)	8·01 × 10−3	1·09 (1·03–1·16)	2·92 × 10−3	−0·023 (0·009)	0·014
Smoking behaviour: heavy vs never smokers
rs4466874, Chr11:112861434		NCAM1	T/C (C)	0·998	NA	0·385 (37 709)	1·10 (1·07–1·13)	3·22 × 10−12	NA	NA	NA	NA
rs10193706, Chr2:146316319		TEX41/ PABPC1P2	A/C (A)	0·983	NA	0·473 (46 280)	1·09 (1·06–1·12)	1·10 × 10−10	NA	NA	NA	NA
rs143125561; rs57342388, Chr20:31162590		NOL4L	C/CACGG (CACGG)	0·983	NA	0·233 (22 820)	1·10 (1·07–1·13)	4·65 × 10−9	NA	NA	NA	NA
rs61784651‖, Chr1:99445471		LPPR5	C/T (T)	1·000	NA	0·170 (16 609)	1·10 (1·07–1·14)	2·89 × 10−8	NA	NA	NA	NA
rs10807199, Chr6:38901867		DNAH8	C/T (T)	1·000	NA	0·473 (46 286)	1·08 (1·05–1·11)	3·17 × 10−8	NA	NA	NA	NA

For variants that showed association with extremes of FEV₁ in either heavy smokers or never smokers, the results from both the never smokers and heavy smokers are presented. For variants that had genome-wide significant evidence of association for smoking behaviour (and not for extremes of FEV₁), association with COPD and effect on FEV₁ were not assessed. Chromosome and position relate to National Center for Biotechnology Information build 37 (hg19). ..=as above. COPD=chronic obstructive pulmonary disease. FEV₁=forced expiratory volume in 1 s. MAC=minor allele count. MAF=minor allele frequency. NA=not applicable. OR=odds ratio. SE=standard error.

^*Indication of certainty of imputation for this variant; an imputation info score of 1 suggests a variant imputed with the highest certainty or a directly genotyped variant.

^†In samples included in the comparison.

^‡Analysis of Global Initiative for Chronic Obstructive Lung Disease stage 2+ COPD cases versus controls (heavy smokers: 5803 cases vs 4661 controls; never smokers: 3761 cases vs 4792 controls).

^§Effect on FEV₁ beta values are effect-size estimates on an inverse-normal transformed scale after adjustments for age, age², sex, height, and ancestry principal components (appendix p 21).

^¶Novel signals of association within previously reported loci.

^‖Directly genotyped.