| Application: | 12505, Dissecting the genetic basis of relationships between early-life and later-life events |
| Title: | Dissection of genetic variation and evidence for pleiotropy in male pattern baldness |
| Size: | 552637 B |
| Archived: | 30 Nov 2020 |
| Stability: | Complete |
| Personal: | No individual-level data |
Return 2904
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Notes
Public interest in male pattern baldness is rooted in cosmetic concern. However, baldness is also worth studying interesting for its interesting combination of biological characteristics: it is strongly hairitable , sex-limited, age-related and common, affecting 80% of Caucasian males. Genetically-speaking, baldness is a complex trait, meaning that there are a multitude of contributing genetic and environmental factors. These characteristics make baldness an attractive trait to study. Why does it only occur in males? Why is baldness so predictably patterned: from scalloped temples and hairline retreat, to thinning crown, to the dreaded end-stage horseshoe ? And how heritable is it? Is your maternal grandfather s dratted X-chromosome really to blame?We studied the genetics of male pattern baldness genetics in 205,327 European males from the UK Biobank. We found that baldness is strongly genetic up to 62% heritable. Common genetic variants accounted for almost 40% of heritability, meaning that most of the variants that contribute to baldness are widely spread throughout the population. However, the more baldness-associated variants one has, the more likely that they will go bald.
We also found that the genetic variants contributing to baldness are numerous, rather than being from a few rare mutations. 624 independent regions scattered across the genome were robustly associated with increased risk of baldness. We were particularly interested in the X-chromosome as it is often neglected in genetic analyses, yet altered androgen receptor sensitivity is associated with baldness. Of the 624 associated regions, 26 were on the X-chromosome, and these made a disproportionate contribution to the heritability.
We looked for whether baldness shares a genetic basis with other traits. Interestingly, there was consistent correlation between increased baldness severity and earlier puberty onset in both sexes (exhibited by facial hair onset and age of voice breaking in males, age of menarche in females, and reduced growth spurt in both sexes). There were also unexpected genetic correlations with increased bone mineral density and pancreatic beta-cell function. These genetic correlations may plausibly be explained by shared androgen pathways. There were also suggestive correlations with reproductive traits such as fewer number of children fathered in males, and fewer live births and increased age of first birth in females. They collectively imply a weak association between increased baldness severity and reduced reproductive fitness.
Overall, we provide genetic insights into baldness: a trait of interest in its own right, with additional value as a model sex-limited, complex trait.
Application 12505
Dissecting the genetic basis of relationships between early-life and later-life events
Differences among individuals in distinct changes in their physiology as they age lead to differences in their susceptibility to negative later-life outcomes, and ultimately to differences in lifespan. This proposal aims to test whether genetic differences among individuals influence changes in cognition and physiological function in later life, to identify the genomic regions and biochemical pathways associated with these changes, and to test for genetic associations between early-life reproduction and later-life outcomes. This is crucial to understanding and predicting transitions across different human life stages. Understanding the genetic basis of relationships between early-life phenotypes, reproductive events, and later-life outcomes is of considerable research and public health interest. This proposal will identify new genetic relationships among physiological and cognitive functions, identify genomic regions of age-specific effect, estimate genetic relationships among life stages, and test the effects of genetic homozygosity in the genome in humans across life. It will lead to a better understanding of the genetic factors and biochemical pathways underlying cognitive and physiological decline in people as they age. Establishing robust genetic links between early and later-life health outcomes is challenging as (i) it usually requires studying people across their lives, and, when using families, (ii) relationships are confounded by other factors, such as shared environment between relatives. A novel design for studying the genetics of ageing will be used, so that even when different traits are measured on different individuals, the genetic basis of changes across life can be studied unbiased of shared environment. This enables an assessment of the genomic basis of multiple later-life phenotypes across different ages, testing theories for the genetics of ageing. For sufficient power to accurately estimate genetic relationships between characters, we require access to the full cohort. Even though individuals in the UKBiobank sample are measured across different ages, we can utilize the estimated genetic relationships among them to ask whether the genetic basis of characters is consistent across later life. We can then assess whether variation in genetic effects across life alters genetic relationships among characters throughout life (i.e., do the impacts of early-life on cognitive or physiological function only become apparent in individuals over 65). This requires data on all individuals recorded across all ages.
| Lead investigator: | Professor Peter Visscher |
| Lead institution: | University of Queensland |
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1 Publication
| Pub ID | Title | Author(s) | Year | Journal |
|---|---|---|---|---|
| 2905 | Dissection of genetic variation and evidence for pleiotropy in male pattern baldness | Chloe X. Yap (+7) | 2018 | Nature Communications |
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