sleep epidemiology, genetics & neurophysiology

Brigham & Women's Hospital, Harvard Medical School, Boston


A near-complete list of publications is available from my Google Scholar page.

Selected manuscripts

Selected manuscripts illustrating past and current work, all with either a first or senior authorship from the Purcell lab, although much of this work was produced within the context of large consortia involving many collaborators.

Characterizing sleep's EEG spectral slope
Sources of Variation in the Spectral Slope of the Sleep EEG

Kozhemiako et al. (eNeuro, 2022) [PDF]

In over 10,000 NSRR PSGs we we validate the EEG spectral slope as a neurobiological marker of cortical arousal across wake, NREM and REM sleep, and report sources of intra-individual and inter-individual variability, including changes across the lifespan.


NREM spectral biomarkers of schizophrenia
Non-rapid eye movement sleep and wake neurophysiology in schizophrenia

Kozhemiako et al. (eLife, 2022) [PubMed | PDF ]

In a collaboration with the Broad Institute and others, we characterized NREM neurophysiological deficits in schizophrenia.


Linking sleep and cognition in older adults
Macro and micro sleep architecture and cognitive performance in older adults

Djonlagic et al. (Nature Human Behaviour, 2021) [PubMed | PDF ]

This study pointed to multiple facets of sleep neurophysiology that track coherently with underlying, age-dependent determinants of cognitive and physical health trajectories in older adults.


Illustrative NREM sleep power spectra in MZ twins and unrelateds
Characterizing sleep spindles in 11,630 individuals from the National Sleep Research Resource

Purcell et al. (Nature Communications, 2017) [PubMed | PDF]

As a prelude to future molecular genetic studies, here we characterize the considerable variation, both between and within individuals, in sleep spindle activity.


Exome sequencing in schizophrenia
A polygenic burden of rare disruptive mutations in schizophrenia

Purcell et al. (Nature, 2014) [PubMed | PDF]

Exome sequencing over 5,000 Swedish individuals to map schizophrenia alleles, genes and networks. Summary statistics are available here.


De novo mutations in schizophrenia
De novo mutations in schizophrenia implicate synaptic networks

Fromer et al. (Nature, 2014) [PubMed | PDF]

Using next-generation exome sequencing in over 600 families to determine the role of newly arising mutations in schizophrenia. Summary statistics are available here.


PLINK: a tool set for whole-genome association and population-based linkage analyses

Purcell et al. (American Journal of Human Genetics, 2007) [PubMed | PDF]

This describes PLINK, a widely used software package for genome-wide association studies. We also introduced a novel approach to genome mapping based on identity-by-descent (IBD) information between very distantly related individuals.


Polygenic risk profiles
Common polygenic variation contributes to risk of schizophrenia and bipolar disorder

International Schizophrenia Consortium (Nature, 2009) [PubMed | PDF]

One of the first large-scale genome-wide association studies of schizophrenia, here we made the observation that many common variants of very small effect appear to contribute to the heritability of schizophrenia. Most of these risk alleles are individually unlikely to be detectable, at least at currently feasible sample sizes.


XHMM pipeline
Discovery and statistical genotyping of copy-number variation from whole-exome sequencing depth

Fromer et al. (American Journal of Human Genetics, 2012) [PubMed | PDF]

Reliably calling copy number variation from targeted sequencing data can be challenging. Here we present and evaluate a robust pipeline that overcomes many of the challenges that arise when trying to infer ploidy from sequencing read depth in exome sequencing studies.


Rare microdeletions
Rare chromosomal deletions and duplications increase risk of schizophrenia

International Schizophrenia Consortium (Nature, 2008) [PubMed | PDF]

Using genome-wide single nucleotide polymorphism arrays, we demonstrated an increased genome-wide burden of rare deletions and duplications (copy number variants, CNV) in patients with schizophrenia compared to controls. We also identified specific genomic loci at which CNVs pile up, namely 22q11, 15q13 and 1q21. [commentaries here and here]


Statistical power and significance testing
Power calculations and significance testing in genetic studies

Sham & Purcell (Nature Reviews Genetics, 2014) [PubMed | PDF]

An introduction and review of the issues around significance testing and power calculation in large-scale genetic studies.


Models of pleiotropy
Pleiotropy in complex traits: challenges and strategies.

Solovieff et al. (Nature Reviews Genetics, 2013) [PubMed | PDF]

This Review considers approaches and interpretations of the often "one-to-many" nature of genotype-to-phenotype associations in complex disease. Nadia Solovieff was a postdoctoral researcher in the Purcell lab, jointly with Dr. Jordan Smoller's group.


Calcium channel A1C sub-unit
Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder

Ferreira et al. (Nature Genetics, 2008) [PubMed | PDF]

This manuscript was the first meta-analysis of genome-wide single nucleotide polymorphism (SNP) data across studies of bipolar disorder. We implicated several genomic regions, including a role for calcium ion channel genes in this disease. [commentary]


Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4

Sklar et al. (Nature Genetics, 2012) [PubMed | PDF]

A later combined analysis of over 15,000 individuals, performed within the context of the PGC, provided further support for calcium channel and other genes.


Variance components twin models
Variance components models for gene-environment interaction in twin analysis

Purcell (Twin Research, 2002) [PubMed | PDF]

A relatively old publication, included here to indicate some of our earlier work in behavioral genetics and twin studies. This manuscript provided a comprehensive methodological treatment for modeling how measured environmental variables can modify the relative impact of genetic influences for quantitative traits.


Genetic Power Calculator
Genetic Power Calculator: design of linkage and association genetic mapping studies of complex traits

Purcell et al. (Bioinformatics, 2003) [PubMed | PDF]

A small application note that describes a simple but widely used web tool for power calculation in the context of genetic association and linkage studies.