# Unlocking Ethiopia’s genomic landscape and its global significance: a call for inclusive genomics research

**Authors:** Sisay Teka Degechisa, Tesfaye B. Mersha

PMC · DOI: 10.1186/s40246-025-00878-8 · Human Genomics · 2026-01-29

## TL;DR

Ethiopia's rich genetic diversity offers unique insights into human evolution and adaptation, but it remains underrepresented in global genomics research.

## Contribution

The paper emphasizes the importance of including Ethiopian populations in genomics research to uncover novel genetic adaptations and improve precision medicine.

## Key findings

- Ethiopia's populations show genetic adaptations to high and low altitudes, lactase persistence, and UV exposure.
- Inclusion of Ethiopian genetic data can enhance global understanding of human evolution and improve clinical outcomes.
- Ethiopia's genetic diversity is underrepresented in current genomic studies, limiting broader scientific insights.

## Abstract

Ethiopia, located at the intersection of Africa and Eurasia, is a hub of human genetic diversity and cultural richness. Its proximity to the Middle East has historically positioned it as a vital trade corridor connecting Asia, Europe, and Africa. Located along both the “out of Africa” and “back to Africa” human migration routes, Ethiopia has become one of the most genetically, ethnically, culturally and linguistically diverse countries in the world. This diversity is further shaped by adaptations to a wide range of environments, from the peaks of the Semien Mountains (4550 m or 14,928 feet above sea level) to the arid Danakil depression (100 m or 328 feet below sea level), both of which harbor rich fauna and flora. Despite its strategic location and rich genetic diversity, Ethiopian populations remain underrepresented in global genomics research. This review: (1) highlights key examples of genetic adaptations that shape the Ethiopian gene pool, including positive selection for high- and low-altitude adaptation, lactase persistence, UV exposure, disease resistance, sour taste perception, and metabolism, and (2) calls for genetics studies that incorporate the unique genetic evolutionary history of the Ethiopian population, which can generate important scientific insights. In the era of precision medicine, it is essential to include genetically diverse populations, such as Ethiopia’s, to ensure the advancement of clinical medicine for everyone.

## Full-text entities

- **Genes:** TMPRSS2 (transmembrane serine protease 2) [NCBI Gene 7113] {aka PRSS10}, CXCL17 (C-X-C motif chemokine ligand 17) [NCBI Gene 284340] {aka DMC, Dcip1, UNQ473, VCC-1, VCC1}, CYP1A2 (cytochrome P450 family 1 subfamily A member 2) [NCBI Gene 1544] {aka CP12, CYPIA2, P3-450, P450(PA)}, PAFAH1B3 (platelet activating factor acetylhydrolase 1b catalytic subunit 3) [NCBI Gene 5050] {aka PAFAHG}, MICU1 (mitochondrial calcium uptake 1) [NCBI Gene 10367] {aka CALC, CBARA1, EFHA3, MPXPS, ara CALC}, THRB (thyroid hormone receptor beta) [NCBI Gene 7068] {aka C-ERBA-2, C-ERBA-BETA, ERBA2, GRTH, NR1A2, PRTH}, BHLHE41 (basic helix-loop-helix family member e41) [NCBI Gene 79365] {aka BHLHB3, DEC2, FNSS1, SHARP1, hDEC2}, IFNA17 (interferon alpha 17) [NCBI Gene 3451] {aka IFN-alphaI, IFNA, INFA, LEIF2C1}, RCC1 (regulator of chromosome condensation 1) [NCBI Gene 1104] {aka CHC1, IIAAN, RCC1-I}, SAA1 (serum amyloid A1) [NCBI Gene 6288] {aka PIG4, SAA, TP53I4}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, AKR1A1 (aldo-keto reductase family 1 member A1) [NCBI Gene 10327] {aka ALDR1, ALR, ARM, DD3, HEL-S-6}, MRC1 (mannose receptor C-type 1) [NCBI Gene 4360] {aka CD206, CLEC13D, CLEC13DL, MMR, MRC1L1, bA541I19.1}, HBB (hemoglobin subunit beta) [NCBI Gene 3043] {aka CD113t-C, ECYT6, beta-globin}, MTHFR (methylenetetrahydrofolate reductase) [NCBI Gene 4524], TMEM138 (transmembrane protein 138) [NCBI Gene 51524] {aka HSPC196}, IFNA14 (interferon alpha 14) [NCBI Gene 3448] {aka IFN-alphaH, LEIF2H}, ADH1A (alcohol dehydrogenase 1A (class I), alpha polypeptide) [NCBI Gene 124] {aka ADH1}, CYP2C9 (cytochrome P450 family 2 subfamily C member 9) [NCBI Gene 1559] {aka CPC9, CYP2C, CYP2C10, CYPIIC9, P450-2C9, P450IIC9}, DDB1 (damage specific DNA binding protein 1) [NCBI Gene 1642] {aka DDBA, UV-DDB1, WHIKERS, XAP1, XPCE, XPE}, LIPE (lipase E, hormone sensitive type) [NCBI Gene 3991] {aka AOMS4, FPLD6, HSL, LHS, REH}, CUL3 (cullin 3) [NCBI Gene 8452] {aka CUL-3, NEDAUS, PHA2E}, G6PD (glucose-6-phosphate dehydrogenase) [NCBI Gene 2539] {aka CNSHA1, G6PD1}, GCG (glucagon) [NCBI Gene 2641] {aka GLP-1, GLP1, GLP2, GRPP}, TLR10 (toll like receptor 10) [NCBI Gene 81793] {aka CD290}, PRDX1 (peroxiredoxin 1) [NCBI Gene 5052] {aka MSP23, NKEF-A, NKEFA, PAG, PAGA, PAGB}, SLC24A5 (solute carrier family 24 member 5) [NCBI Gene 283652] {aka JSX, NCKX5, OCA6, SHEP4}, LCT (lactase) [NCBI Gene 514332], MFSD12 (major facilitator superfamily domain containing 12) [NCBI Gene 126321] {aka C19orf28, PP3501, SLC59B1}, NEGR1 (neuronal growth regulator 1) [NCBI Gene 257194] {aka DMML2433, IGLON4, KILON, Ntra}, TLR1 (toll like receptor 1) [NCBI Gene 7096] {aka CD281, TIL, TIL. LPRS5, rsc786}, HLA-A (major histocompatibility complex, class I, A) [NCBI Gene 3105] {aka HLAA}, HBA2 (hemoglobin subunit alpha 2) [NCBI Gene 3040] {aka ECYT7, HBA-T2, HBH}, FOLR1 (folate receptor alpha) [NCBI Gene 2348] {aka FBP, FOLR, FR-alpha, FRalpha, NCFTD}, IFNA1 (interferon alpha 1) [NCBI Gene 3439] {aka IFL, IFN, IFN-ALPHA, IFN-alphaD, IFNA13, IFNA@}, CIC (capicua transcriptional repressor) [NCBI Gene 23152] {aka MRD45}, RBPJ (recombination signal binding protein for immunoglobulin kappa J region) [NCBI Gene 3516] {aka AOS3, CBF-1, CBF1, IGKJRB, IGKJRB1, KBF2}, CNFN (cornifelin) [NCBI Gene 84518] {aka PLAC8L2}, VKORC1 (vitamin K epoxide reductase complex subunit 1) [NCBI Gene 79001] {aka EDTP308, MST134, MST576, VKCFD2, VKOR}, EGLN1 (egl-9 family hypoxia inducible factor 1) [NCBI Gene 54583] {aka C1orf12, ECYT3, HALAH, HIF-PH2, HIFPH2, HPH-2}, NUMB (NUMB endocytic adaptor protein) [NCBI Gene 8650] {aka C14orf41, S171, c14_5527}, CYP3A4 (cytochrome P450 family 3 subfamily A member 4) [NCBI Gene 1576] {aka CP33, CP34, CYP3A, CYP3A3, CYPIIIA3, CYPIIIA4}, BNC2 (basonuclin zinc finger protein 2) [NCBI Gene 54796] {aka BSN2, LUTO, bn2}, CYP4F3 (cytochrome P450 family 4 subfamily F member 3) [NCBI Gene 4051] {aka CPF3, CYP4F, CYPIVF3, LTB4H}, EPAS1 (endothelial PAS domain protein 1) [NCBI Gene 2034] {aka ECYT4, HIF2A, HLF, MOP2, PASD2, bHLHe73}, SAA4 (serum amyloid A4, constitutive) [NCBI Gene 6291] {aka C-SAA, CSAA}, CYP3A5 (cytochrome P450 family 3 subfamily A member 5) [NCBI Gene 1577] {aka CP35, CYPIIIA5, P450PCN3, PCN3}, VAV3 (vav guanine nucleotide exchange factor 3) [NCBI Gene 10451], ACE2 (angiotensin converting enzyme 2) [NCBI Gene 59272] {aka ACEH}, CDKAL1 (CDKAL1 threonylcarbamoyladenosine tRNA methylthiotransferase) [NCBI Gene 54901], HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091] {aka HIF-1-alpha, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1}, ADH1B (alcohol dehydrogenase 1B (class I), beta polypeptide) [NCBI Gene 125] {aka ADH2, HEL-S-117}, IFNA16 (interferon alpha 16) [NCBI Gene 3449] {aka IFN-alpha-16, IFN-alphaO}, TLR6 (toll like receptor 6) [NCBI Gene 10333] {aka CD286}, CORO1B (coronin 1B) [NCBI Gene 57175] {aka CORONIN-2}, CBLIF (cobalamin binding intrinsic factor) [NCBI Gene 2694] {aka GIF, IF, IFMH, INF, TCN3}, PKD2L1 (polycystin 2 like 1, transient receptor potential cation channel) [NCBI Gene 9033] {aka PCL, PKD2L, PKDL, TRPP3}, HERC2 (HECT and RLD domain containing E3 ubiquitin protein ligase 2) [NCBI Gene 8924] {aka D15F37S1, MRT38, SHEP1, jdf2, p528}, ZRANB3 (zinc finger RANBP2-type containing 3) [NCBI Gene 84083] {aka 4933425L19Rik, AH2}, LDHA (lactate dehydrogenase A) [NCBI Gene 3939] {aka GSD11, HEL-S-133P, LDHM, PIG19}
- **Diseases:** P, vivax malaria (MESH:D016780), HIV-associated (MESH:D016263), LP (MESH:D007787), viral infections (MESH:D014777), Hypoxia (MESH:D000860), plague (MESH:D010930), metabolic dysregulation (MESH:D021081), P. falciparum malaria (MESH:D016778), nutritional deficiencies (MESH:D044342), lactase persistence (MESH:C562600), malaria (MESH:D008288), immune-mediated diseases (MESH:C567355), ESRD (MESH:D007676), HbS (MESH:D000755), warfarin resistance (MESH:C563039), metabolic diseases (MESH:D008659), polycythemia (MESH:D011086), inflammation (MESH:D007249), kidney disease (MESH:D007674), sickle cell trait (MESH:D012805), CMS (MESH:D000532), helminth infections (MESH:D007239), autoimmune conditions (MESH:D001327), obesity (MESH:D009765), G6PD deficiency (MESH:D005955), African sleeping sickness (MESH:D014353), hemoglobinopathies (MESH:D006453), alcoholism (MESH:D000437), neural tube defects (MESH:D009436), sarcoidosis (MESH:D012507), anemia (MESH:D000740), lymphedema (MESH:D008209), hemolytic anemia (MESH:D000743), folate deficiency (MESH:C562799), infectious disease (MESH:D003141), volcanic eruption (MESH:D003875), Trypanosomiasis (MESH:D014352), cancer (MESH:D009369), HIV (MESH:D015658), T2DM (MESH:D003924), alpha-thalassemia (MESH:D017085), alpha-thalassaemia (MESH:D000795), darker skin pigmentation (MESH:D010859), hypoxic (MESH:D002534), leprosy (MESH:D007918), toxicity (MESH:D064420), Visceral Leishmaniasis (MESH:D007898), celiac disease (MESH:D002446), HA (MESH:C535833), light skin pigmentation (MESH:C567155), tuberculosis (MESH:D014376), asthma (MESH:D001249)
- **Chemicals:** codeine (MESH:D003061), caffeine (MESH:D002110), ethanol (MESH:D000431), 5 Methyl tetrahydrofolate (MESH:C005984), carbohydrate (MESH:D002241), O2 (MESH:D010100), olanzapine (MESH:D000077152), homocysteine (MESH:D006710), starch (MESH:D013213), lactose (MESH:D007785), clozapine (MESH:D003024), Folic acid (MESH:D005492), Warfarin (MESH:D014859), alcohol (MESH:D000438), nitrofurantoin (MESH:D009582), fatty acid (MESH:D005227), lipid (MESH:D008055), fluvoxamine (MESH:D016666), polycyclic aromatic hydrocarbons (MESH:D011084), sugar (MESH:D000073893), glucose (MESH:D005947), melatonin (MESH:D008550), nitric oxide (MESH:D009569), -malarial (-), estradiol (MESH:D004958), melanin (MESH:D008543), acetaldehyde (MESH:D000079), primaquine (MESH:D011319)
- **Species:** Bos taurus (bovine, species) [taxon 9913], Ebola virus [taxon 186536], Plasmodium falciparum (malaria parasite P. falciparum, species) [taxon 5833], Trypanosoma brucei rhodesiense (subspecies) [taxon 31286], Plasmodium vivax (malaria parasite P. vivax, species) [taxon 5855], Homo sapiens (human, species) [taxon 9606], Human immunodeficiency virus 1 (no rank) [taxon 11676], Glossina (tsetse flies, genus) [taxon 7393], Yersinia pestis (species) [taxon 632]
- **Mutations:** ss820486563, rs2229616, C677T, Asp36Tyr, -14010G>C, rs2815752, rs1801282, rs9939609, rs1426654, rs41525747, rs1229984, G202A, rs10946398, rs7903146, rs236514, R378W, rs41380347, T-13910, rs2814778, -14009T>G, C563T, R278Q, rs1834640

## Full text

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## References

9 references — full list in the complete paper: https://tomesphere.com/paper/PMC12857168/full.md

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Source: https://tomesphere.com/paper/PMC12857168