Our research aims at identifying genes that contribute to individual variation in the risk of complex disease. We work towards this aim by
- Mapping genomic regions contributing to disease risk, and
- Developing systems genetic approaches to identify genes and pathways under the control of these genetic risk factors.
Our work finds application in precision medicine, public health, and drug development.
We have a particular interest in longitudinal phenotypes, such as BMI and its relation to childhood obesity. We identified genes regulating variation in children’s growth and discovered two distinct genetic components for infant and child BMI. We were awarded funds for one PhD Project to expand this work in collaboration with Surrey’s Math department, Southampton University, and the Born in Bradford Study. We work in articulation with the Early Growth Genetics consortium, where we contribute to the longitudinal phenotypes group. Through our collaboration with Prof. Andre Gerber, we develop systems genetics approaches to understand the contribution of post-transcriptional regulation to the downstream effects of genetic risk factors.
Areas of specialism
University roles and responsibilities
- Head of Bioinformatics Core Facility
- Genome wide association studies (GWAS)
- Expression quantitative trail loci studies (eQTL, GxE-eQTL)
- Gene expression association studies
- Statistical modeling of health data
- Regression and graphical models (stan)
- Variable selection, and Model averaging
- Applied machine learning to health and biological data
- DNA-Seq: Genotype calling, and quality control
- RNA-Seq: Alignment and quantification
- Genotype SNP arrays: Genotype calling and quality control
Software in the areas of my research specialism can be found at https://github.com/acoutoal
In the media
We develop bioinformatics methods and strategies to identify genes and pathways involved in human disease. The goal is to identify the genes networks and developmental time windows involved in disease susceptibility, and in doing so to guide intervention strategies improving population health. We have extensive experience coordinating, designing, and running genome wide association studies, gene expression association studies, and mapping expression quantitative trait loci. We has developed software and visualization tools widely used in genomics and molecular epidemiological studies for multi-omics data integration, DNA-Seq variant calling, RNA-Seq quantification, gene expression analysis, metabolomics protocol optimization and biomarker discovery. We has developed predictive models of molecular and clinical markers applied to disease prognosis and diagnosis.
Prof. John Holloway, Southampton University
Prof. John Wright, Born in Bradford Study
Dr Naratip Santissa, University of Surrey
Prof. Marjo-Riitta Jarvelin, Imperial College
Indicators of esteem
Personal research awards and fellowships
2018 Research Fellow, School of Public Health, Imperial College London
2015 Research Fellow, Dept of Twin Research and Genetic Epidemiology, King’s College London
2007 PhD Fellowship of the Portuguese National Science and Technology Foundation
Keynote and plenary addresses at conferences
2014 Systems biology and functional analysis of disease genes. European academy of allergy and clinical immunology congress.
2007 Co-chair Workshop on Computational Methods in Bioinformatics and Systems Biology. As part of the Portuguese Conference on Artificial
2005 Co-chair Workshop on Computational Methods in Bioinformatics. As part of the Portuguese Conference on Artificial Intelligence.
- Journal of the Royal Statistical Society
- International Journal of Epidemiology
- International Journal of Allergy and Clinical Immunology
- Nature Scientific Reports
- Nature Communications Biology
- Genome Medicine
- Annals of Human Genetics
Completed postgraduate research projects I have supervised
2019. Christopher Shore. MSc Thesis: Mendelian Randomisation of Birthweight on Adult Blood Lipids, the University of Surrey. Currently pursuing a PhD at King's College London.
2014, Ricardo Pinho. MSc Thesis: Machine learning methodologies for gene-gene interactions discovery in complex disease, the University of Porto
2013, Nikman Nor Ashim. MSc Thesis: Identification of copy number variants associated with fasting plasma glucose, Imperial College London. Currently, Senior Lecturer at the University of Malaya.
2006, Nuno Castro. MEng Thesis (Lic.): Prediction of rare events in sequence data, Minho University. Currently, Director of Data Science at Expedia.
2005, Hugo Penedones. MEng Thesis (Lic.): Anomaly detection in time series, University of Porto. Currently, the Founder of Inductiva Research Labs.
Postgraduate research supervision
2021. Nadia Mohammed. PhD Microbiology. Antibiotic Resistance.
2020. Noushin Saadullahkhani. MSci Biochemistry. Mendelian Randomisation of Adiponectin on Diabetes Melitius.
I teach human genetics, genomics and bioinformatics in the following modules:
- MOLECULAR BIOLOGY AND GENETICS
- SYSTEMS BIOLOGY
- MICROBIAL GENETICS AND MOLECULAR BIOLOGY
Couto Alves, A., De Silva, N. M. G., Karhunen, V. , Sovio, U., Das, S., et al. GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI. Science Advances (2019).
Couto Alves, A.; Glastonbury, CA; Moustafa, JSES; Small, KS Fasting and time of day independently modulate circadian rhythm relevant gene expression in adipose and skin tissue. BMC genomics (2018)
Demenais, F., Margaritte-Jeannin, P., Barnes, K. C., Cookson, W. O., Altmüller, J., Ang, W., Barr, R. G., Beaty, T. H., Becker, A. B., Beilby, J., et al. Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks. Nature genetics 50, 1 (2018), 42.
Liu, D. J., Peloso, G. M., Yu, H., Butterworth, A. S., Wang, X., Mahajan, A., Saleheen, D., Emdin, C., Alam, D., Couto Alves, A., et al. Exome-wide association study of plasma lipids in> 300,000 individuals. Nature genetics 49, 12 (2017), 1758.
Ried, J. S., Chu, A. Y., Bragg-Gresham, J. L., Van Dongen, J.,Huffman, J. E., Ahluwalia, T. S., Cadby, G., Eklund, N., Eriksson, J., Esko, T., et al. A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape. Nature communications 7 (2016), 13357.
Paternoster, L., Standl, M., Waage, J., Baurecht, H., Hotze, M., Strachan, D. P., Curtin, J. A., Bønnelykke, K., Tian, C., Takahashi, A., et al. Multi-ethnic genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis. Nature genetics 47, 12 (2015), 1449
Kato, N., Loh, M., Takeuchi, F., Verweij, N., Wang, X., Zhang, W., Kelly, T. N., Saleheen, D., Lehne, B., Leach, I. M., et al. Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for dna methylation. Nature genetics 47, 11 (2015), 1282–1293
Loth, D. W., Artigas, M. S., Gharib, S. A., Wain, L. V., Franceschini, N., Koch, B., Pottinger, T. D., Smith, A. V., Duan, Q., Oldmeadow, C., et al. Genome-wide association analysis identifies six new loci associated with forced vital capacity. Nature genetics 46, 7 (2014), 669–677.
Bønnelykke, K., Matheson, M. C., Pers, T. H., Granell, R., Strachan, D. P., Couto Alves, A., Linneberg, A., Curtin, J. A., Warrington, N. M., Standl, M., et al. Meta-analysis of genomewide association studies identifies ten loci influencing allergic sensitization. Nature genetics 45, 8 (2013), 902–906.
Paternoster, L., Standl, M., Chen, C.-M., Ramasamy, A., Bønnelykke, K., Duijts, L., Ferreira, M. A., Couto Alves, A., Thyssen, J. P., Albrecht, E., et al. Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis. Nature genetics 44, 2 (2012), 187–192.
Early childhood growth patterns are associated with adult health, yet the genetic factors and the developmental stages involved are not fully understood. Here, we combine genome-wide association studies with modeling of longitudinal growth traits to study the genetics of infant and child growth, followed by functional, pathway, genetic correlation, risk score, and colocalization analyses to determine how developmental timings, molecular pathways, and genetic determinants of these traits overlap with those of adult health. We found a robust overlap between the genetics of child and adult body mass index (BMI), with variants associated with adult BMI acting as early as 4 to 6 years old. However, we demonstrated a completely distinct genetic makeup for peak BMI during infancy, influenced by variation at the LEPR/LEPROT locus. These findings suggest that different genetic factors control infant and child BMI. In light of the obesity epidemic, these findings are important to inform the timing and targets of prevention strategies.
Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1, PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.
You may find an updated list of publications at my google scholar profile