Genome-based prediction of common diseases: methodological considerations for future research

Janssens, A Cecile JW; van Duijn, Cornelia M

doi:10.1186/gm20

Table 2 Methodological characteristics of recent studies on the prediction of complex diseases using multiple genes*

From: Genome-based prediction of common diseases: methodological considerations for future research

First author (year) and reference	Design	Cases	Controls^†	n (cases/controls)^‡	Variant selection^§	Analyses	Evaluation	Calibration	Validation	Compared with clinical prediction
Cauchi (2008) [10]	Case-control	T2D	Normal glucose-tolerant individuals (screened)	4,232/4,595	From GWAS in same population	LR	Distribution RASs, OR for RASs, AUC	No	No	No
Harley (2008) [28]	Case-control	Women with SLE	Age-matched women without SLE	720/2,337	From GWAS in same population	LR	AUC	No	No	No
Humphries (2007) [15]	Prospective cohort	Coronary heart disease	Caucasian men	183/1,874	4 (out of 12) candidate genes	Cox PH, weighted risk score, risk score	Kaplan-Meier curves, AUC	No	No	Yes
Kathiresan (2008) [18]	Prospective cohort	Myocardial infarction, ischemic stroke and death from coronary heart disease	General population	238/3,994	9 (out of 11) candidate SNPs in 9 genes	Cox PH, RAS	Distribution RASs, incidence rates for RASs, Kaplan-Meier curves, AUC, reclassification	No	No	Only added value^¶
Lango (2008) [11]	Case-control	T2D	Normoglycemic (screened)	2,309/2,598	18 established variants	LR, RAS	Distribution RASs, OR for RASs, AUC	No	No	Yes
Lyssenko (2005) [30]	Prospective cohort	T2D	Relatives and spouses	132/2,161	3 (out of 6) SNPs in 5 genes	Cox PH	HR for genotype combinations	No	No	No
Lyssenko (2008) [21]	Prospective cohort	T2D	Two cohorts: general population and non-diabetic relatives	2,201/16,630	11 (out of 16) established variants	LR, RAS	Distribution RASs, incidence rates for RASs, AUC, reclassification	No	No	Yes
Maller (2006) [13]	Case-control	Advanced AMD	Individuals without AMD or early AMD	1,238/934	5 (out of 1,536 tag SNPs) in candidate genes	LR	Relative risk for genotype combinations^¥	No	No	No
Meigs (2008) [22]	Prospective cohort	T2D	Offspring of general population cohort	255/2,122	18 established variants	LR, RAS	Distribution RASs, incidence rates for RASs AUC, reclassification	Yes	No	Yes
Morrison (2007) [16]	Prospective cohort	Coronary heart disease	General population	1,452/12,455	11 (out of 116) SNPs	Cox PH, RAS	Distribution RASs, AUC	No	Internal	Only added value
Podgoreanu (2006) [26]	Prospective cohort	Myocardial infarction	Patients undergoing elective cardiac surgery with cardio-pulmonary bypass	52/382	3 (out of 48) SNPs in 23 candidate genes	LR	AUC	No	No	Yes
Van der Net (2009) [17]	Prospective cohort	Coronary heart disease	FH patients	387/950	14 SNPs previously associated	Cox PH, RAS	Predicted risk for RASs, AUC	No	No	Yes
Van Hoek (2008) [14]	Prospective cohort	T2D	General population	1,287/5,221	18 established variants	Cox PH, LR, RAS	Predicted risks for RASs, OR of RASs, AUC	No	No	Yes
Vaxillaire (2008) [27]	Prospective cohort	T2D	General population	307/3,570	3 (out of 19) SNPs in 14 candidate genes	LR	OR of RAS, AUC	No	No	Yes
Wang (2008) [12]	Case-control	Severe hypertriglyceridemia	Normolipidemic controls	132/351	7 established variants	LR	AUC Hosmer-Lemeshow goodness of fit		No	Only added value
Weedon (2006) [19]	Case-control	T2D	Individuals without T2D, including one normoglycemic subpopulation	2,409/3,668	3 established variants	LR, RAS	Distribution RASs, OR of RASs, AUC	No	No	No
Weersma (2008) [23]	Case-control	Chronic inflammatory bowel disease	Healthy controls	2,804/1,350	5 established genes	LR, RAS	OR of RASs	No	No	No
Yeh (2007) [25]	Case-control	Colorectal cancer	Healthy controls	727/736	3 (out of 10) established variants	LR	OR for genotype combinations^¥	No	No	No
Zheng (2008) [20]	Case-control	Prostate cancer	General population	2,893/1,781	5 (out of 16) SNPs in 5 candidate regions	LR, genotype score	Distribution genotype score, AUC, PAR	No	No	No

*Abbreviations: AMD, age-related macular degeneration; AUC, area under the receiver operating characteristic curve, sometimes measured by the c-statistic; Cox PH, Cox proportional hazard regression analysis; FH, familial hypercholesterolemia; GWAS, genome-wide association studies; HR, hazard ratio; LR, logistic regression; OR, odds ratio; PAR, population attributable risk; RAS, risk allele score; SLE, systemic lupus erythematosus; SNP, single nucleotide polymorphism; T2D, type 2 diabetes. ^†For prospective cohort studies, this column describes the total population from which the cases were obtained. ^‡For prospective cohort studies, these numbers indicate the number of cases divided by the number of individuals who did not develop the disease during follow-up. ^§Numbers between parentheses indicate the total number of variants at the start of the analysis from which the most predictive variants were selected. Candidate means that the variants were selected from the literature, on the basis of association with disease risk in other studies. ^¶This study compared prediction from clinical risk factors with clinical risk factors plus genetic factors, but did not consider prediction from genetic factors alone. ^¥These studies did not intend to evaluate the predictive value, but investigated the combined effect of multiple variants on disease risk.

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ISSN: 1756-994X

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