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Male Pattern Baldness GWAS Uncovers New Loci, Potential Links to Other Complex Traits

NEW YORK (GenomeWeb) – An international team has identified dozens of new loci linked to male pattern baldness, contributing to a collection of loci that appear to explain more than one-third of the heritability behind this trait.

As they reported today in Nature Communications, researchers from the University of Edinburgh, the University of Tartu, and elsewhere performed a genome-wide association study involving more than 70,000 men, including more than 43,590 individuals with or without male pattern baldness from the UK Biobank — a resource that a UK team tapped for a smaller GWAS on male pattern baldness published in PLOS Genetics earlier this year.

That team used the same UK Biobank data to create a prediction score for male pattern baldness, and did not seek replication, corresponding and co-first author Nicola Pirastu, a population health sciences and informatics researcher at the University of Edinburgh, and his colleagues wrote. Notably, their own team was unable to replicate several loci found in the previous study and detected 34 additional ones. "These differences are probably due to the different phenotypic definition in the two studies and to the different nature of the study design," they wrote

After the discovery stage of the study and validation in several independent cohorts — including 23andMe participants — the team was left with 71 loci with apparent ties to male pattern baldness, also known as androgenetic alopecia.

Past research suggests androgen hormone response is a factor in male pattern baldness, the team explained, though several other pathways and processes may contribute as well — including those with potential ties to other traits or conditions.

"[D]espite numerous described co-morbidities with [male pattern baldness], the biology responsible for these correlations remain largely unknown," Pirastu and colleagues wrote.

For their study, the researchers began by comparing patterns at more than 27.5 million directly genotyped or imputed SNPs in 25,662 UK Biobank participants with self-reported British ancestry and male pattern baldness and 17,928 without, leading to nearly 12,200 SNPs with significant ties to male pattern baldness in the discovery group.

The team verified associations for 11,624 SNPs through validation testing on another 16,824 male pattern baldness cases and 14,288 unaffected controls, including non-British UK Biobank participants, 23andMe research participants, and European American participants from the "Atherosclerosis Risk in Communities" (ARIC) study and the "Health Professionals Follow-up Study" (HPFS).

These variants fell in around 71 loci, including 30 sites not previously implicated in male pattern baldness, the researchers reported. Along with the androgen receptor signaling, the loci were overrepresented in parts of the genome with apparent ties to everything from developmental regulation or apoptosis to Wnt signaling or other signaling processes.

Along with network analyses to detect interacting genes falling into baldness-associated loci, the team took a look at potential pleiotropy between loci linked to baldness and those contributing to other traits or conditions — an analysis that pointed to correlation between genetic contributors to male pattern baldness and those implicated in height, male lifespan, and cancer risk.

"[D]espite only showing genome-wide correlation with height, pathway-specific genetic correlations are significant for trait including lifespan and cancer," the authors wrote. "Our study not only greatly increases the number of [male pattern baldness] loci, illuminating the genetic architecture, but also provides a new approach to disentangling the shared biological pathways underlying complex diseases."

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