Table 2 Study design, population characteristics and outcomes of hypothesis-generating pharmacogenetic studies investigating anthracycline-induced cardiotoxicity in patients with osteosarcoma

Aminkeng et al., 2015

GWAS

Stage 1: 11 (of 280)

Cases: 7.5 (2.5 – 15.5)

Controls: 9 (7 – 12)

Caucasian; Canadian

738,432 variants

RARG rs2229774

[48]

Stage 2: 9 (of 96)

Cases: 22 (19 – 25)

Controls: 17 (14 – 22)

Caucasian; Dutch

Stage 3: 5 (of 80)

Cases: 15.5 (7 – 22)

Controls: 10 (7 – 15)

African, East Asian and Aboriginal

Chaix et al., 2020

Exome sequencing

Disc.30^a of 289

Cases: 8.5 (5.0 – 12.3)

Controls: 9.0 (6.0 – 12.3)

NS

110,558 variants in 17,382 genes

n/a

[24]

Hildebrandt et al., 2017

Hypertension loci

41 (of 108)

Cases: 21.2 (SD: 11.2)

Controls: 15.7 (SD: 7.6)

White, hispanic or black; American

12 variants in PLCE1, ATP2B1, ARHGAP42, GNAS-EDN3, C10orf107, CSK, BAG6, CACNB2, MTHFR, CACNB2, HFE, NPR3

PLCE1 rs932764^*

[47]

ATP2B1 rs17249754^*

Ruiz-Pinto et al., 2017

Exome array with low frequency variants

15 (of 93)

Cases: 10.5 (1 – 27.5)

Controls: 8.3 (1 – 24.1)

NS; Spanish

247,870 variants

GPR35 rs12468485

[49]

Sapkota et al., 2021

Whole genome sequencing

NS

NS

Disc.: African

9.3 million common variants (MAF ≥ 0.05) and 10.2 million rare/low frequency variants (MAF ≤ 0.05)

1p13.2 rs6689679

[23]

Repl.: European

15q25.3 rs9788776

Sapkota et al., 2021

Whole genome sequencing

NS

NS

Disc.: European

6.69 million common variants (MAF ≥ 0.05) and rare/low frequency variants (MAF ≤ 0.05) number NS

6p21.2 rs2815063

[22]

Repl 1.: African

Repl. 2.: European

Visscher et al., 2012

ADME panel

Disc.: 11 (of 156)

Cases: 6.5 (0.1 – 21.5)

Controls: 7.8 (5.0 – 17.9)

Disc. and repl.: (non-) European; Canadian

Repl.2: NS; Dutch

1,931 variants in 220 drug bio-transformation genes

SLC28A3 rs7853758

[50]

Repl.: 10 (of 188)

Cases: 7.4 (0.2 – 20.7)

Controls: 9.2 (5.0 – 18.6)

Repl.2: 6 (of 96)

Cases: 20.2 (7.4 – 27.9)

Controls: 15.4 (5.1 – 29.8)

Visscher et al., 2015

ADME panel

Discover.: 21 (of 344)

NS

NS; Canadian and Dutch

4,153 variants in 300 pharmacokinetics and -dynamics genes

SLC22A17 rs4982753^*

[51]

Repl.: 16 (of 218)

SLC22A7 rs4149178^*

Wang et al., 2014

Cardiovascular panel: gene – environment interaction

Disc.: 54^a (of 287)

Cases: 10.0 (0.1 – 35.1)

Controls: 11.3 (0.9 – 41.0)

Disc.: Non-Hispanic white; American

34,912 variants in 2,100 genes associated with cardiovascular disease

HAS3 rs2232228

[52]

Repl.: 0 (of 76)

4.0 (0.5 – 22.5)

Repl.: Non-Hispanic white, Hispanic, other; American

Wang et al., 2016

GWAS: gene – environment interaction

Disc.: 96^b (of 331)

Cases: 9.4 (0.1–35.1)

Controls: 12.9 (1.4–41)

Disc.: Non-Hispanic white; American

709,358 variants

CELF4 rs1786814

[53]

Repl.: 17 (of 54)

Repl.: Non-Hispanic white, Hispanic, Other; American

Windsor et al., 2012

Pathway approach

58 (of 58)

41 (12–93) months

Caucasian, Afro-Caribbean, Indian, Asian; UK

35 variants in 21 pharmacological pathway genes of MAP

GSTP1 rs1695^*

[37]