: Application

About

Both common and rare genetic variants contribute to the heritability of complex traits. However, usually they are analysed separately using different analytical techniques, such as single variant regression versus burden methods. This fails to fully utilise the information contained in genomes. Here, we aim to apply computational methods we have developed which combine information from common and rare variants and which can utilise information about the predicted effects of the variants to identify genes influencing complex traits. We will use our results to assess how natural selection has shaped the genetic architecture of complex traits in modern humans. We will particularly focus on non-communicable diseases, such as cardiovascular disease, neurological disorders and cancer, and disease-related traits, such as obesity and cholesterol levels, as well as the susceptibility to infectious diseases. Differences in environments, natural selection and drift may have distinctly shaped the genetic architectures in some populations. Therefore, we will compare results for different ancestry groups.

3 Returns

Return ID	App ID	Description	Archive Date
3787	51119	Analysis of 50,000 exome-sequenced UK Biobank subjects fails to identify genes influencing probability of developing a mood disorder resulting in psychiatric referral	6 Sep 2021
3614	51119	Analysis of exome-sequenced UK Biobank subjects implicates genes affecting risk of hyperlipidaemia	30 Jun 2021
4003	51119	Investigation of Association of Rare, Functional Genetic Variants With Heavy Drinking and Problem Drinking in Exome Sequenced UK Biobank Participants	14 Oct 2021

25 Publications

Pub ID	Title	Author(s)	Year	Journal
10398	Age at Natural Menopause and Blood Pressure Traits: Mendelian Randomization Study	Zayne M. Roa-Díaz (+11)	2021	Journal of Clinical Medicine
4059	Analysis of 200 000 exome-sequenced UK Biobank subjects illustrates the contribution of rare genetic variants to hyperlipidaemia	David Curtis	2021	Journal of Medical Genetics
4061	Analysis of 200,000 Exome-Sequenced UK Biobank Subjects Implicates Genes Involved in Increased and Decreased Risk of Hypertension	David Curtis	2021	Pulse
16397	Analysis of 470,000 exome-sequenced UK biobank participants identifies genes containing rare variants which confer dementia risk	Lily Gibbons (+1)	2025	Journal of Neurogenetics
16371	Analysis of 470,000 exome-sequenced cases and controls fails to identify any genes impacting risk of developing affective disorder	David Curtis	2025	Acta Neuropsychiatrica
3788	Analysis of 50,000 exome-sequenced UK Biobank subjects fails to identify genes influencing probability of developing a mood disorder resulting in psychiatric referral	David Curtis	2020	Journal of Affective Disorders
15397	Analysis of Rare Coding Variants in 470,000 UK Biobank Participants Reveals Genetic Associations With Childhood Asthma Predisposition	Zhenzhen Liu (+1)	2025	International Journal of Immunogenetics
8342	Analysis of Rare Variants in 470,000 Exome-Sequenced UK Biobank Participants Implicates Novel Genes Affecting Risk of Hypertension	David Curtis	2023	Pulse
3615	Analysis of exome-sequenced UK Biobank subjects implicates genes affecting risk of hyperlipidaemia	David Curtis	2020	Molecular Genetics and Metabolism
4069	Analysis of rare coding variants in 200,000 exome-sequenced subjects reveals novel genetic risk factors for type 2 diabetes	David Curtis	2021	Diabetes/Metabolism Research and Reviews
12720	Assessment of ability of AlphaMissense to identify variants affecting susceptibility to common disease	David Curtis	2024	European Journal of Human Genetics
16556	Assessment of ability of a DNA language model to predict pathogenicity of rare coding variants	David Curtis	2025	Journal of Human Genetics
7100	Clinical features of UK Biobank subjects carrying protein-truncating variants in genes implicated in schizophrenia pathogenesis	David Curtis	2022	Psychiatric Genetics
4832	Exploration of weighting schemes based on allele frequency and annotation for weighted burden association analysis of complex phenotypes	David Curtis	2021	Gene
7286	Haploinsufficiency of the HIRA gene may not always produce severe neurodevelopmental consequences	David Curtis	2021	Psychiatric Genetics
16679	Health effects of loss of function variants in gene targets for Alzheimer's disease prevention	Yuan Ma (+3)	2025	Neurological Sciences
5276	Investigation of Association of Rare, Functional Genetic Variants With Heavy Drinking and Problem Drinking in Exome Sequenced UK Biobank Participants	David Curtis	2021	Alcohol and Alcoholism
8756	Investigation of Recessive Effects of Coding Variants on Common Clinical Phenotypes in Exome-Sequenced UK Biobank Participants	David Curtis	2024	Human Heredity
5435	Multiple Linear Regression Allows Weighted Burden Analysis of Rare Coding Variants in an Ethnically Heterogeneous Population	David Curtis	2020	Human Heredity
12254	Study of variants in genes implicated in rare familial migraine syndromes and their association with migraine in 200,000 exome-sequenced UK Biobank participants	Katherine Alexis Markel (+1)	2022	Annals of Human Genetics
9010	UK Biobank subjects carrying protein truncating variants in HERC1 are not at substantially increased risk of minor psychiatric disorders	David Curtis	2024	Psychiatric Genetics
5983	Variants in ACE2 and TMPRSS2 Genes Are Not Major Determinants of COVID-19 Severity in UK Biobank Subjects	David Curtis	2020	Human Heredity
7594	Weighted burden analysis in 200,000 exome-sequenced subjects characterises rare variant effects on BMI	David Curtis	2022	International Journal of Obesity
8546	Weighted burden analysis of rare coding variants in 470,000 exome-sequenced UK Biobank participants characterises effects on hyperlipidaemia risk	David Curtis	2024	Journal of Human Genetics
8610	Welch's t test is more sensitive to real world violations of distributional assumptions than student's t test but logistic regression is more robust than either	David Curtis	2024	Statistical Papers

1 Category

Category ID	Description	Items
100314	Genomics	+280

Title:	Study of effects of common and rare genetic variants on health-related phenotypes
Lead Institution:	University College London
Principal investigator:	Professor David Curtis