statgen-reading.md

Readings in Statistical Genetics

• Articles
• How to keep up with new published articles?
• Journals that publish articles in Statistical Genetics.

Articles

Some key articles on:

• General GWAS
• Summary statistics
• Genetic architecture
• Integration of omics
• Heritability
• Fine-mapping
• Colocalisation
• Mendelian randomisation
• Pleiotropy

Data

• Use of population isolates for mapping complex traits: Nature Reviews Genetics article by Leena Peltonen, Aarno Palotie & Kenneth Lange in 2000. Lays out the fundamental idea of using population isolates to study complex traits.

GWAS

• Genome-wide association studies: An article in Nature Reviews Methods Primer by Uffelmann, E., Huang, Q.Q., Munung, N.S. et al.
• Genome-wide association studies, polygenic scores and social science genetics: overview and policy implications: Technical report by the Joint Research Centre (JRC), the European Commission’s science and knowledge service, by Angers Alexandre, Kagkli Dafni Maria, Koellinger Philipp, Petrillo Mauro, Querici Maddalena, Raffael Barbara and Van den Eede Guy.
• What article to reference as the first GWAS.
• Thinking About the Evolution of Complex Traits in the Era of Genome-Wide Association Studies; Guy Sella and Nicholas H. Barton. 2019.
• A very general introduction to GWAS: Genomewide Association Studies and Human Disease; John Hardy and Andrew Singleton. 2009.
• 10 Years of GWAS Discovery: Biology, Function, and Translation; Peter M. Visscher, Naomi R. Wray, Qian Zhang, Pamela Sklar, Mark I. Mccarthy, Matthew A. Brown, and Jian Yang. 2017.
• Genomics is failing on diversity; Alice B. Popejoy and Stephanie M. Fullerton. 2016.
• Genome-wide association studies for complex traits: consensus, uncertainty and challenges; Mark I. McCarthy, Gonçalo R. Abecasis, Lon R. Cardon, David B. Goldstein, Julian Little, John P. A. Ioannidis and Joel N. Hirschhorn. 2008.
• Finding the missing heritability of complex diseases; Teri A. Manolio, Francis S. Collins, Nancy J. Cox, David B. Goldstein, Lucia A. Hindorff, David J. Hunter, Mark I. McCarthy, Erin M. Ramos, et al.. 2009.
• A tutorial on conducting genome‐wide association studies:Quality control and statistical analysis; Andries T. Marees, Hilde de Kluiver, Sven Stringer, Florence Vorspan, Emmanuel Curis, Cynthia Marie‐Claire, Eske M. Derks. 2018.

Summary statistics

• Dissecting the genetics of complex traits using summary association statistics; Bogdan Pasaniuc, Alkes L. Price. 2017.
• Is Reidentifiability a Risk? Open versus restricted access for summary statistics: Mark J. Daly, 2017.

Genetic architecture

• From gene expression to disease risk; Emmanouil T. Dermitzakis. 2008.
• Genetic architecture: the shape of the genetic contribution to human traits and disease.; Nicholas J. Timpson, Celia M.T. Greenwood, Nicole Soranzo, Daniel J. Lawson, and J. Brent Richards. 2017.
• Common Disease Is More Complex Than Implied by the Core Gene Omnigenic Model.; Naomi R. Wray, Cisca Wijmenga, Patrick F. Sullivan, Jian Yang, Peter M. Visscher. 2018.

Integration of omics data

• Is PRNP associated to any human traits besides prion disease?; Eric Minikel. 2019.

• Integration of summary data from GWAS and eQTL studies predicts complex trait gene targets; Zhihong Zhu, Futao Zhang, Han Hu, Andrew Bakshi, Matthew R Robinson, Joseph E Powell, Grant W Montgomery, Michael E Goddard, Naomi R Wray, Peter M Visscher & Jian Yang. 2016.

• Integrating Gene Expression with Summary Association Statistics to Identify Genes Associated with 30 Complex Traits; Nicholas Mancuso, Huwenbo Shi, Pagé Goddard, Gleb Kichaev, Alexander Gusev, Bogdan Pasaniuc. 2017.

• trans-eQTL blogpost by Greg Gibson (2021).

Heritability

• Explaining additional genetic variation in complex traits; Matthew R. Robinson, Naomi R. Wray, and Peter M. Visscher. 2014.
• Partitioning heritability by functional annotation using genome-wide association summary statistics.; Hilary K Finucane, Brendan Bulik-Sullivan, Alexander Gusev, GosiaTrynka, Yakir Reshef, Po-Ru Loh, Verneri Anttila, et al. (2015). Nature Genetics.
• Reevaluation of SNP heritability in complex human traits; Doug Speed, Na Cai, the UCLEB Consortium, Michael R. Johnson, Sergey Nejentsev, David J. Balding. 2017.
• Concepts, estimation and interpretation of SNP-based heritability; Jian Yang, Jian Zeng, Michael E. Goddard, Naomi R. Wray, Peter M. Visscher. 2017.
• Relationship between LD Score and Haseman-Elston Regression; Brendan Bulik-Sullivan. 2015.

Fine-mapping

• Widespread Allelic Heterogeneity in Complex Traits; Farhad Hormozdiari, Anthony Zhu, Gleb Kichaev, Chelsea J.-T. Ju, Ayellet V. Segrè, Jong Wha J. Joo, Hyejung Won, Sriram Sankararaman, Bogdan Pasaniuc, Sagiv Shifman, Eleazar Eskin. 2017.

• Abundant associations with gene expression complicate GWAS follow-up, Liu, B., Gloudemans, M.J., Rao, A.S. et al. (2019). *Why fine-mapping is essential especially for (e)QTLs. *

Colocalization

• Colocalization of GWAS and eQTL Signals Detects Target Genes; Farhad Hormozdiari, Martijn van de Bunt, Ayellet V. Segrè, Xiao Li, Jong Wha J. Joo, Michael Bilow, Jae Hoon Sul, Sriram Sankararaman, Bogdan Pasaniuc, Eleazar Eskin. 2016.
• A more accurate method for colocalisation analysis allowing for multiple causal variants Wallace C (2021). Latest coloc extension

Mendelian randomisation

• Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression; Jack Bowden, George Davey Smith, Stephen Burgess. 2015. MR-Egger Regression and how it deals with pleiotropy and invalid IV.

• Mendelian randomization: genetic anchors for causal inference in epidemiological studies; George Davey Smith, Gibran Hemani. 2014. Overview of MR and its extensions.

• Mendelian Randomization Analysis With Multiple Genetic Variants Using Summarized Data; Stephen Burgess, Adam Butterworth, Simon G. Thompson. 2013. MR using summarised data, introduces the various MR methods like IVW, likelihood-based and talks about weak instruments and winners curse. Interesting things to know at the start.

• Recent Developments in Mendelian Randomization Studies; Jie Zheng, Denis Baird, Maria-Carolina Borges, Jack Bowden, Gibran Hemani, Philip Haycock, David M. Evans, George Davey Smith. 2017. A very well rounded review on MR, more detailed than the first listed article, recent (late 2017) and discusses applications, limitations, and different extensions of MR.

Pleiotropy

HOPS: a quantitative score reveals pervasive horizontal pleiotropy in human genetic variation is driven by extreme polygenicity of human traits and diseases, Jordan, D.M., Verbanck, M. & Do, R (2019). Good illustration of difference between pleiotropy types.

Misc

• An Abundance of Rare Functional Variants in 202 Drug Target Genes Sequenced in 14,002 People, Nelson et al. (2012).

Other reading lists and resources

Checkout the The Leek group guide to genomics papers. This is more about genomics & RNA sequencing, but has some good background reading.

This online journalclub from the Broad Institute is not active anymore, but has some recordings.

How to keep up with new published research?

1. Create a google scholar alert with keywords of interest. This especially handy to not miss new publications in your own field.
2. Follow journals on social media, e.g. bioRxiv.
3. Follow authors or consortia on social media, e.g. PGC Consortium.
4. Subscribe to journal newsletters (sometimes called e-alerts).
5. Join (the mailing list of) a journal club, e.g. the this one.

Journals

• Nature Genetics
• Nature Reviews Genetics
• American Journal of Human Genetics
• PLoS Genetics
• PLoS Computational Biology
• Bioinformatics
• Genetic Epidemiology
• European Journal of Human Genetics
• bioRxiv = medRxiv
• BMC Genetics
• BMC Genomics
• Genome Biology
• Human Genetics
• Nature
• Nature Communications

This list is not exhaustive. There are lots of other journals that also contain articles on statistical genetics, e.g. Biostatistics.

Contributors

• Sina Rüeger
• Eleonora Porcu
• Emilie Ha
• Liza Darrous