Table 1 Landmark and innovative transethnic genetic association analyses*

Type 2 diabetes

TCF7L2

Haplotype analysis

Replication of primary signal in WA population and fine-mapping of second independent signal showing positive selection in WA, EA and EUR cohorts; recently also replicated in large-scale meta-analysis over 39 studies

[42],[105]

Lipids (HDLC and TGs)

ABCA1, LCAT, LPL, PON1, SERPINE1

Candidate gene resequencing

Fine-mapping of known LPL gene association in AA with extreme lipid phenotypes, replication in WA, and showed stronger effect size of causal variants (local ancestry effects) as compared to EUR

[106]

End-stage kidney disease

APOL1

GWAS

Common variants in APOL1 associated with resistance to Trypanosoma also confer risk for renal disease

[15]

Uric acid levels (serum)

SLC2A9

GWAS

Replication of a 263 kb association locus (identified in EUR) in an AA cohort enabled fine-mapping to a 27 kb shared region

[107]

Bilirubin levels

UGT1A1

GWAS

Replication of previously identified association in this locus in EUR and ASN cohorts using AFR population; also enabled fine-mapping to a functional, putatively causative variant

[108]

ALL

CEBPE, PIP4K2A, ARID5B

GWAS

Known risk-associated variants are more common in NA, confer greater risk and explain the higher observed risk of ALL in Hispanic children. Illustrates how disease risk analysis can shed light on disease associations in admixed populations with complex genomic architectures

[109]

T2D

HNF1A

Exome seq

High-throughput sequencing identified rare, novel missense mutation in a known locus associated with maturity-onset diabetes (MODY3); association is specific to Latino populations. Recently highlighted in a review on admixed population analysis

[82],[110]

Prostate cancer

15 EUR-specific, 7 multi-ethnic

GWAS

Large study encompassing over 40,000 cases and 40,000 controls in EUR, AFR, JPT, and Latino populations; multi-ethnic analyses help identify 7 new signals not found in EUR

[111]

BMI

BRE, DHX34, other

Custom genotyping platform

Metabochip analysis across about 30,000 AA individuals confirms 8 EUR BMI loci in AA, identified independent signal in known locus and identified two novel loci

[112]

Global gene expression levels

Multiple

Expression array

EUR, JPT and CHN populations show large variations in gene expressions due to differences in allele frequencies of common regulatory eSNPs, possibly explaining differences in complex disease risk

[113]

T2D

Multiple

GWAS meta-analysis

Landmark transethnic FE meta-analysis across nearly 27,000 cases from 5 ethnic minority populations identified 7 novel signals, enabled fine-mapping of 10 loci, and demonstrated evidence of heterogeneity compared with EUR studies using MANTRA software

[33]