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Table 1 Landmark and innovative transethnic genetic association analyses*

From: Trans-ethnic genome-wide association studies: advantages and challenges of mapping in diverse populations

Trait Gene or locus Platform Comments References
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]
  1. *GWAS and other forms of genetic association studies have historically and recently provided important insights into disease-related loci. This table highlights a few notable examples, providing the study phenotypes, key associations (where specific), and details of the study including any unique approach used and the main findings/advances. Abbreviations: AA, African American; AFR, African; ALL, acute lymphoblastic leukemia; ASN, Asian; BMI, body mass index; CEU, Caucasoid; CHN, Chinese; EA, East Asian; eSNP, expression single nucleotide polymorphism; EUR, European; FE, fixed effects; GWAS, genome-wide association study; HDLC, high density lipoprotein cholesterol; JPT, Japanese; LD, linkage disequilibrium; NA, Native American; RE, random effects; T2D, type 2 diabetes; TG, triglycerides; WA, West African.