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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
  1. *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.