Daniel E Weeks

Contributions to Public Health

• My research focuses on statistical human genetics in the area of mapping susceptibility loci involved in complex diseases. His My primary interest is developing new mapping methods, which involves developing algorithms and statistics, implementing them in computer programs, and testing them on real and simulated data. In addition, he isI am actively involved in a number of collaborative human genetics projects, all of which constantly challenge him me to develop new and more useful methods for dealing with the complexities of real data. He isI am studying the genetic influences on obesity, lipids, and body composition. In addition, he I and his my colleagues are studying the effects of methylation on patient recovery outcomes after traumatic brain injury, and on cognitive function within the context of treatment for breast cancer.
• Statistical genetics methodology: A major focus of my career has been on the development and refinement of new statistical methods for mapping risk genes, which involves developing algorithms and statistics, implementing them in computer programs, and testing them on real and simulated data. We have used functional linear models to create more powerful gene-based association statistics (1a), as well as kernel-based methods for testing for association with multivariate quantitative traits (1b).
  • Jiang Y, Chiu CY, …, Weeks DE, Fan R. Gene-based association testing of dichotomous traits with generalized functional linear mixed models using extended pedigrees: Applications to age-related macular degeneration. J Am Stat Assoc. 2021;116(534):531-545. PMCID: PMC8315575.
  • Yan Q, Weeks DE, Celedón JC, Tiwari HK, Li B, Wang X, Lin WY, Lou XY, Gao G, Chen W, Liu N. Associating multivariate quantitative phenotypes with genetic variants in family samples with a novel kernel machine regression method. Genetics. 2015 Oct 19;PMID: 26482791; PMCID: PMC4676518.  
• Genetics of complex human diseases: linkage, association, prediction. In addition to developing methodology, I have been and am actively involved in a large number of collaborative disease gene mapping projects, all of which constantly challenge me to develop new and more useful methods for dealing with the complexities of real data. We used the principles of linkage and association to study the genetics of adiposity in Samoans (2a), food allergy, chemotherapy symptom clusters, and recovery from traumatic brain injury.
  • Minster RL, Hawley NL, Su CT, …, Urban Z, Deka R, Weeks DE, McGarvey ST. (2016) A thrifty variant in CREBRF strongly influences body mass index in Samoans. Nat Genet. 48(9):1049-54.; PMCID: PMC5069069.
• Genetics of complex human diseases: epigenomics. We are studying epigenomic effects on neurocognitive function in breast cancer patients, after aneurysmal subarachnoid hemorrhage (3b), and after traumatic brain injury. In all our work, we pay very careful attention to issues of quality control (3a).
  • Buhule OD, Minster RL, Hawley NL, Medvedovic M, Sun G, Viali S, Deka R, McGarvey ST, Weeks DE. Stratified randomization controls better for batch effects in 450K methylation analysis: a cautionary tale. Front Genet. 2014;5:354. PMID: 25352862; PMCID: PMC4195366.
  • Heinsberg LW, Weeks DE, Alexander SA, Minster RL, Sherwood PR, Poloyac SM, Deslouches S, Crago EA, Conley YP (2021) Iron homeostasis pathway DNA methylation trajectories reveal a role for STEAP3 metalloreductase in patient outcomes after aneurysmal subarachnoid hemorrhage. Epigenetics Commun 1. PMCID: PMC8788201
• Statistical genetics software: Novel statistical methodology is only useful if it is implemented in well-working computer programs. Over my career, we have created many useful analysis programs for the research community, including Pedcheck for checking family data for Mendelian inconsistencies, Vitesse for rapid LOD score analysis, FastSLINK for simulation of genetic data on pedigrees, Mega2 and Mega2R for easing tedious file format conversions, and dbVOR, a database system for managing genetic data.  See also https://danieleweeks.github.io/Daniel_E_Weeks/software/
  • O'Connell JR, Weeks DE. PedCheck: a program for identification of genotype incompatibilities in linkage analysis. Am J Hum Genet. 1998 Jul;63(1):259-66. PMID: 9634505; PMCID: PMC1377228.
  • Baron RV, Stickel JR, Weeks DE. The Mega2R package: R tools for accessing and processing genetic data in common formats. F1000Res. 2018;7:1352. PubMed PMID: 30271589; PMCID: PMC6137409.
• Mentorship & training: Over my career, I have mentored or co-mentored numerous students and postdoctoral scholars (5a-b). I have also served as Program Director of a T32 post-doctoral training grant (co-directed by Bernie Devlin) and a Fogarty-funded US-India training grant (co-directed by Partha Majumder). I also directed an annual Wellcome Genome Campus Advanced Course on statistical genetics from 1996-2022.  See also https://danieleweeks.github.io/Daniel_E_Weeks/team/   †Graduate student; ‡Post-doctoral scholar.
  • Heinsberg LW‡, Weeks DE (2022) Post hoc power is not informative. Genet Epidemiol 46:390-394. PMID: 35642557; PMCID: PMC9452450.
  • Liu S†, Fu H†, Ray M, Heinsberg LW‡, Conley YP, Anderson CM, Hubel CA, Roberts JM, Jeyabalan A, Weeks DE, Schmella MJ. A longitudinal epigenome-wide association study of preeclamptic and normotensive pregnancy. Epigenetics Commun. 2023;3(1):1. PMCID: PMC10101051.