Opportunities and Challenges in the Genetics of COPD 2010: An International COPD Genetics Conference Report

Figures & data

Table 1  International COPD Genetics Consortium study populations—Genetics

		Current sample size			Genome-wide SNP genotyping availability
Study name	Study type	All COPD	Severe COPD	Control	All COPD	Severe COPD	Control	Estimated final sample size for genetic studies	Genome-wide SNP genotyping platform	Country	Race/ethnicity	Ref
ANOLD**	Case-Only	1011	431	0	0	0	0	1,200	None	Nine asian countries	All Asian
COPACETIC	Case-Control	1029	46	1958	1029	46	1958	15,000	Illumina 610	Europe	All White	(56)
COPDGene**	Case-Control	3590	1791	4131	2481	1189	3014	10,000	Illumina omni-express	USA	2/3 non- Hispanic Whites (NHW) and 1/3 African Americans (AA)	(57)
COSYCONET**	Case-Control	3000	1500	>5000	0	0	0	>6000	Not determined	Germany	All White
ECLIPSE	Case-Control	1839	1003	196	1839	1003	196	2043	Illumina 550	Europe, N. America, Australia	All White	(58)
EU COPD/East midlands consortium	Case-Control	1616	1050	912	0	0	0	2528	Not determined	Europe	All White	(59)
EvA**	Case-Control	290	78	230	0	0	0	1,200	Illumina	Europe	All White
GenKOLS	Case-Control	933	386	919	933	386	919	1853	Illumina 550	Norway	All White	(12)
Hokkaido	Case-Control	274	45	150	0	0	0	500	None	Japan	All Asian	(60)
ICE COLD	Case-Only	411	142	0	0	0	0	411	None	Switzerland/ Netherlands	All White	(61)
KOLD**	Case-Control	321	134	305	0	0	0	700 COPD Cases	None	Korea	All Asian	(62)
Leuven	Case-Control	800	400	300	0	0	0	1,250	Not applicable	Belgium	All White	(19)
Lung Health Study	Case-Only	5887	0	0	4126	0	0	4191	Illumina 660W	USA and Canada	4126 Whites, 65 AA	(63)
New Zealand	Case-Control	458	277	488	0	0	0	946	Not applicable	New Zealand	All White	(18)
NETT	Case-Only	366	366	0	366	366	0	366	Illumina 610	USA	All White	(43)
PAC COPD	Case-Only	342	159	0	0	0	0	342	0	Spain	All White	(64)
SPIROMICS**	Case-Control	0	0	0	0	0	0	3200	Not Determined	USA	Not Determined	–
Transcontinental: Korea**	Case-Control	80	80	179	0	0	0	600	None	Korea	All Asian	–
Transcontinental: Poland	Case-Control	302	302	333	0	0	0	635	None	Poland	All White	–
Wake Forest	Case-Control	490	192	509	490 (in 2011)	192 (in 2011)	509 (in 2011)	1,000	Illumina	USA	91% White 8% AA	(65)
Atherosclerosis Risk in Communities (ARIC)^+,^#	Pop-Based	1194	586	8337	943	481	6602	7545	Affymetrix 6.0 + IBC chip (Both Whites and African Americans)	USA	White	(15)
		247	155	3315	185	30	1607	1792			African American
Cardiovascular Health Study (CHS)^+,^#	Pop-Based	402	292	2183	402	292	2183	2585	Illumina 370CNV beadchip + IBC chip (Both Whites and African Americans)	USA	White^+	(15)
		123	31	277	123	31	277	400			African American^#
Cleveland Family Study^#	Family/Pop-Based	17	4	203	0	0	0	220	IBC chip	USA	White^#
		29	4	159	29	4	159	188	IBC chip ^+ Affymetrix 6.0		African American^#
Copenhagen City Heart	Pop-Based	∼2000	n/a	∼8000	0	0	0	∼10,000	None	Denmark	n/a
Copenhagen General Population	Pop-Based	∼6000	n/a	∼54,000	0	0	0	∼60,000	None	Denmark	n/a
Coronary Artery Risk Development in Young Adults (CARDIA)^#	Pop-Based	31	2	1148	0	0	0	1179	IBC chip	USA	White^#
		25	2	969	25	2	969	994	IBC chip ^+ Affymetrix 6.0		African American^#
EMCAP	Pop-Based	200	n/a	450	0	0	0	657	None	USA	70% White, 10% AA, 10% Hispanic, 10% Asian	(66)
Framingham Heart Study^+^#	Family/Pop-Based	571	274	5866	571	274	5866	6437	Affymetrix 500 + 50K gene-centric chip	USA	All White^#	(14)
Jackson Heart Study^#	Pop-Based	182	36	1982	182	36	1982	2164	Affymetrix 6.0 + IBC chip	USA	African American^#
Lifelines	Family/Pop-Based	592	10	2506	592	10	2506	20,000	Illumina Human Cyto SNP-12 V2	Netherlands	Mostly White	(67)
Lovelace Smokers Cohort	Pop-Based	500	100	1700	0	0	0	2900	None	USA	20% Hisp 80% NHW	(68)
Multi-Ethnic Study of Atherosclerosis (MESA) lung study^+,^#	Pop-Based	384	53	2651	∼350	∼50	∼2500	3965	Affymetrix 6.0 + IBC chip	USA	35% NHW,^# 25% AA^# 25% Hisp^# 15% Asian^#	(69)
MESA Lung SHARe	Family/Pop-Based	‡	‡	‡	‡	‡	‡	4200	Affymetrix 6.0	USA	30%
											NHW^#,
											30% AA^#
											30% Hisp^#
											10% Asian^#
Normative Aging Study	Pop-Based	191	n/a	1024	0	0	472	1215	Illumina 610	USA	All White	(17, 27)
Rotterdam Study (RS1, RS2 and RS3 combined)^+	Pop-Based	209	136	2672	209	136	2672	2881	Illumina Infinium II 550K	Netherlands	All White	(15)
SpiroMeta^++	Pop-Based	3278	n/a	17,523	356	n/a	3,730	63,079	Multiple GWAS platforms (n = 24, 756); multiple non-GWAS platforms (n = 38, 314)	Europe and Australia	All White	(16)
Vlagtwedde/ Vlaardingen	Pop-Based	351	27	991	0	0	0	1342	None	Netherlands	All White	(70)
		Probands	Relatives		Probands	Relatives
Boston Early-Onset COPD	Family	200	∼1000		0	0		1200	None	USA	98% White	4
International COPD Genetics Network	Family	983	1876		0	0		2859	None	North America and Europe	Mostly White	(71)

*Note that “All COPD” and “Control” were defined differently within each study and/or consortium. “Severe COPD” was defined as GOLD 3–4 using post-bronchodilator spirometry if available, and pre-bronchodilator spirometry if not available. For the CHARGE consortium studies, severe COPD was defined as noted below.

**Indicates that study population is still being recruited.

⁺Participating in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium which includes only Whites from these cohorts. In CHARGE, COPD was defined as FEV₁<LLN and FEV₁/FVC<LLN. Severe COPD was defined as FEV₁/FVC < LLN and FEV₁ < 65% Predicted. Controls were defined by FEV₁, FEV₁/FVC and FVC all > LLN.

#Participating in the Candidate Gene Association Resource (CARe) consortium (72). For African Americans in CARe, “COPD” was defined as pre-BD ratio <0.70 and FEV1%pred<80%; “severe COPD” as pre-BD ratio <0.70 and FEV1%pred <50%; and controls as pre-BD ratio >0.70 and FEV1%pred >80%. Note that for cohorts participating in both CHARGE and CARe, definitions of COPD, severe COPD, and control status used in this table differ for Caucasians and African-Americans from the same participating cohort. Additionally, for the ARIC cohort, case and control counts for the total (“current”) sample of African-Americans are based on the CHARGE definitions rather than the CARe definitions.

⁺⁺SpiroMeta–Cases: FEV₁ <80% predicted and FEV₁/FVC <0.7; Controls FEV₁>80% predicted and FEV₁/FVC ratio of >0.7. Numbers of individuals known to be cases and known to be controls are shown (further data collection is underway; the number of known COPD cases and documented controls will increase when this information is received).

^‡Characterized with CT scan only.

Table 2  International COPD Genetics Consortium study populations—Phenotypes

				Spirometry		Chest CT			Other Phenotypes
Study	Age Range	Gender (% Male)	Minimum Pack-Years	Pre-BD	Post-BD	Obtained?	Visual Assessment	Quantitative Assessment	Exac**	Co- Mor**	Lung Function Decline
ANOLD	40–91	94	10	Yes	Yes	No	–	–	Yes	Yes	No
COPACETIC	50–80	98	20	Yes	Some	Yes	No	Yes	Yes	No	Yes
COPDGene	45–80	52	10	Yes	Yes	Yes	No	Yes	Yes	Yes	No
COSYCONET	>40	n/a	0	Yes	Yes	Some	Yes	Yes	Yes	Yes	Yes
ECLIPSE	40–75	66	10	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
EU COPD/East Midlands Consortium	Mean 66	70	10	Yes	Yes	No	–	–	No	Yes	Some
EvA	45–75	65	5	Yes	Yes	Yes	No	Yes	No	Yes	No
GenKOLS	40–81	66	2.5	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Some
Hokkaido	41–87	94	12	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
ICE COLD	Mean 66	57	0	No	Yes	No	–	–	Yes	Yes	Yes
KOLD	45–82	92	10	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
Leuven	43–90	75	15	Yes	Yes	Yes	Yes	No	Yes	Yes	No
Lung Health Study	35–60	63	10	Yes	Yes	No	–	–	Yes	Some	Yes
New Zealand	40–85	60	15	Yes	No	No	–	–	No	Yes	No
NETT	Mean 67	73	0	Yes	Yes	Yes	Yes	Yes	Yes	Yes	No
PAC COPD	Mean 68; Range 44–86	93	0	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
SPIROMICS	TBD	TBD	TBD	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
Transcontinental: Korea	40–80	97	10	Yes	Yes	No	–	–	Yes	Yes	No
Transcontinental: Poland	40–80	69	10	Yes	Yes	No	–	–	Yes	Yes	No
Wake Forest	42–88	96	20	Yes	No	No	–	–	No	Yes	Yes
ARIC	45–64	45	0	Yes	No	No	–	–	Yes	Yes	Yes
Cardiovascular Health Study	65–95	43	0	Yes	No	No	–	–	No	Yes	Yes
Cleveland Family Study	23–88	48	0	Yes	No	No	–	–	No	Yes	No
Copenhagen City Heart	n/a	n/a	0	Yes	n/a	No	–	–	Yes	Yes	n/a
Copenhagen General Population	n/a	n/a	0	Yes	n/a	No	–	–	Yes	Yes	?
CARDIA	27–44	45	0	Yes	No	No	–	–	No	Yes	Yes
EMCAP	>60	50	10	Yes	Some	Yes	Yes	Yes	Yes	Yes	Yes
Framingham	19–92	46	0	Yes	Some	In Subset	Pending	Pending	No	Yes	Yes
Jackson Heart Study	21–93	38	0	Yes	No	No	–	–	No	Yes	No
Lifelines	21–88	41	0	Yes	No	No	–	–	No	Yes	No
Lovelace Smokers Cohort	40–75	22	15	Yes	Yes	No	–	–	Yes	Yes	Yes
MESA Lung	45–84	49	0	Yes	Some	Yes	Pending	Yes	Yes	Yes	Pending
MESA Lung SHARe	45–84	50	0	No	No	Yes (cardiac)	No	Yes	No	Yes	No
Normative Aging Study	21- >80	100	0	Yes	No	No	–	–	No	Yes	Yes
Rotterdam Study	>45	45	0	Yes	No	No	–	–	No	Yes	Pending (RS1)
SpiroMeta	8–93	42	0	Yes	In a subset	No	–	–	No	No	No
Vlagtwedde/ Vlaardingen	35–79	51	0	Yes	No	No	–	–	No	Some	Yes
Boston Early-Onset COPD	>10	42	0	Yes	Yes	No	–	–	Yes	Yes	No
International COPD Genetics Network	45–65	46	5	Yes	Yes	In Subset	Yes	Yes	Yes	Yes	No

*For a subset of individuals (n = 20, 288) with information on age and gender currently available.

**Abbreviations: “Exac” = Data available regarding COPD exacerbations; “CoMor” = Data available regarding co-morbid diseases.

Table 3  International COPD Genetics Consortium: Approximate current study population sample sizes

	Cases	Controls
Case-Control Studies (or Case-Only Studies)	23,039	15,610
Cohort Studies	16,526	115,956
Combined Set	39,565	131,566
GWAS in Combined Set Currently Available	14,741	37,612

Notes: For this table, approximate sample sizes from Table 1 were used as actual values. Only subjects with spirometry from Table 1 were included in these calculations (MESA Lung SHARe was excluded). Population-based studies with a family component (e.g., Framingham) are listed under “Cohort Studies,” while other pedigree-based studies (e.g. International COPD Genetics Network) have been excluded. For the “GWAS in Combined Set Currently Available,” only subjects with available genotyping by December 2010 were included.

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