Uncovering the genetic architecture and evolutionary roots of androgenetic alopecia in African men

Androgenetic alopecia is a highly heritable trait. However, much of our understanding about the genetics of male-pattern baldness comes from individuals of European descent. Here, we examined a dataset comprising 2,136 men from Ghana, Nigeria, Senegal, and South Africa that were genotyped using the Men of African Descent and Carcinoma of the Prostate Array. We first tested how genetic predictions of baldness generalize from Europe to Africa and found that polygenic scores from European genome-wide association studies (GWASs) yielded area under the curve statistics that ranged from 0.513 to 0.546, indicating that genetic predictions of baldness generalized poorly from European to African populations. Subsequently, we conducted an African GWAS of androgenetic alopecia, focusing on self-reported baldness patterns at age 45. After correcting for age at recruitment, population structure, and study site, we identified 266 moderately significant associations, 51 of which were independent (p < 10<sup>-5</sup>, r<sup>2</sup> < 0.2). Most baldness associations were autosomal, and the X chromosome does not seem to have a large impact on baldness in African men. Although Neanderthal alleles have previously been associated with skin and hair phenotypes, within the limits of statistical power, we did not find evidence that continental differences in the genetic architecture of baldness are due to Neanderthal introgression. While most loci that are associated with androgenetic alopecia do not have large integrative haplotype scores or fixation index statistics, multiple baldness-associated SNPs near the EDA2R and AR genes have large allele frequency differences between continents. Collectively, our findings illustrate how population genetic differences contribute to the limited portability of polygenic predictions across ancestries.

Authors

Institutions

Publication Details

Journal
Human Genetics and Genomics Advances
Published
2025-03-25
DOI
https://doi.org/10.1016/j.xhgg.2025.100428
Citations
3
Primary Topic
Hair Growth and Disorders
Type
article
Field-Weighted Citation Impact
5.51

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Uncovering the genetic architecture and evolutionary roots of androgenetic alopecia in African men

Maxine Harlemon, Akindele O. Adebiyi, Rohini Janivara, P. Fernandez et al.
3 citations
Human Genetics and Genomics Advances
Hair Growth and Disorders
5.51
article

Uncovering the genetic architecture and evolutionary roots of androgenetic alopecia in African men

Maxine Harlemon, Akindele O. Adebiyi, Rohini Janivara, P. Fernandez, Ben Adusei, James Edward Mensah, Caroline Andrews, Wenlong Carl Chen, Muthukrishnan Eaaswarkhanth, Andrew A. Adjei, Joseph Lachance, Paidamoyo Kachambwa, Lindsay N. Petersen, Aaron Pfennig, Ilir Agalliu, Mohamed Jalloh, Thomas E. Rohan, Michelle S. Kim, Adebola Ogunbiyi, Timothy Richard Rebbeck, Ujani Hazra, Oseremen I. Aisuodionoe-Shadrach, Maureen Joffe, Serigne M. Gueye
article en
3 citations

Abstract

Androgenetic alopecia is a highly heritable trait. However, much of our understanding about the genetics of male-pattern baldness comes from individuals of European descent. Here, we examined a dataset comprising 2,136 men from Ghana, Nigeria, Senegal, and South Africa that were genotyped using the Men of African Descent and Carcinoma of the Prostate Array. We first tested how genetic predictions of baldness generalize from Europe to Africa and found that polygenic scores from European genome-wide association studies (GWASs) yielded area under the curve statistics that ranged from 0.513 to 0.546, indicating that genetic predictions of baldness generalized poorly from European to African populations. Subsequently, we conducted an African GWAS of androgenetic alopecia, focusing on self-reported baldness patterns at age 45. After correcting for age at recruitment, population structure, and study site, we identified 266 moderately significant associations, 51 of which were independent (p < 10<sup>-5</sup>, r<sup>2</sup> < 0.2). Most baldness associations were autosomal, and the X chromosome does not seem to have a large impact on baldness in African men. Although Neanderthal alleles have previously been associated with skin and hair phenotypes, within the limits of statistical power, we did not find evidence that continental differences in the genetic architecture of baldness are due to Neanderthal introgression. While most loci that are associated with androgenetic alopecia do not have large integrative haplotype scores or fixation index statistics, multiple baldness-associated SNPs near the EDA2R and AR genes have large allele frequency differences between continents. Collectively, our findings illustrate how population genetic differences contribute to the limited portability of polygenic predictions across ancestries.

Human Genetics and Genomics AdvancesVol. 6(3)
National Health Laboratory Service (ZA), Albert Einstein College of Medicine (US), Georgia Institute of Technology (US), University of Ghana (GH), Georgia State University (US), University of Ibadan (NG), University of the Witwatersrand (ZA), Stellenbosch University (ZA), Korle Bu Teaching Hospital (GH), Dana-Farber Cancer Institute (US), African Organisation for Research and Training in Cancer (ZA), Dana-Farber/Harvard Cancer Center (US), 37 Military Hospital (GH), Université de Thiès (SN), University of Abuja (NG), Morgan State University (US), Cheikh Anta Diop University (SN)
National Cancer Institute, National Institute of General Medical Sciences
Zero hunger
Openalex Percentile: Top 5%
Hair Growth and Disorders
5.51
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.