| Application: | 9072, The Genetics of anthropometric traits ? Height, weight, BMI and waist circumference |
| Title: | Genome-wide association analyses of chronotype in 697,828 individuals provides insights into circadian rhythms |
| Size: | 5.4 MB |
| Archived: | 14 Jan 2020 |
| Stability: | Complete |
| Personal: | Contains individual-level data |
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Notes
Being a morning person is a behavioural indicator of a person's underlying circadian rhythm. Using genome-wide data from 697,828 UK Biobank and 23andMe participants we increased the number of genetic loci associated with being a morning person from 24 to 351. Using data from 85,760 UK Biobank participants with activity-monitor derived measures of sleep timing we found that the chronotype loci associate with sleep timing: the mean sleep timing of the 5% of individuals carrying the most morningness alleles was 25 minutes earlier than the 5% carrying the fewest. The loci were enriched for genes involved in circadian regulation, cAMP, glutamate and insulin signalling pathways, and those expressed in the retina, hindbrain, hypothalamus, and pituitary. Using Mendelian Randomisation, we show that being a morning person is causally associated with better mental health but does not affect BMI or risk of Type 2 diabetes. This study offers insights into circadian biology and its links to disease in humans.Application 9072
The Genetics of anthropometric traits ? Height, weight, BMI and waist circumference
Our question is `what are the genetic factors that lead to altered height, weight, BMI, waist-circumference and adiposity in today?s environment?? We will identify the genetic factors that: i) influence height ? a measure of growth in childhood. ii) influence weight, BMI, waist-circumference and adiposity. Excess adiposity predisposes individuals to common diseases including diabetes and heart disease. There is a genetic component to where people lie on the BMI scale. We will use UK Biobank to identify more of the genetic factors. iii) influence blood pressure, heart disease and diabetes through genetic effects on growth, BMI or adiposity. Our proposed research will address a fundamental health question - why are some individuals more overweight than others in today's obesogenic environment whilst others do not? There is very strong evidence that genetic factors account for some of these differences between individuals and yet we have not identified a large component of the genetic heritability of BMI, adiposity and obesity. We also argue that studying height provides an exemplar trait to assess the ability of genetic technologies and methods to identify the genetic components to common human traits. Our proposal will proceed in two phases. In phase 1 we will analyse all the genetic variants measured in the initial 150,000 individuals. We will analyse the approximately 800,000 genetic variants against BMI, height, weight, adiposity measures in all 150,000 individuals and against intermediate traits that may influence these outcomes, including diet, activity and exercise. We will use genetic variants associated with adiposity and metabolic traits to assess their role in metabolic disease outcomes such as type 2 diabetes, heart disease and hypertension. In phase2 we will repeat these analyses but using the dataset of 500,000. In phase 1 the 150,000 currently with genotype data and in phase 2 the full 500,000.
| Lead investigator: | Professor Tim Frayling |
| Lead institution: | University of Exeter |
1 Publication
| Pub ID | Title | Author(s) | Year | Journal |
|---|---|---|---|---|
| 1863 | Genome-wide association analyses of chronotype in 697,828 individuals provides insights into circadian rhythms | Samuel E. Jones (+31) | 2019 | Nature Communications |
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