Daria V. Zhernakova

@article{Wu2026-wl,

title = {The interplay of sleep characteristics with health factors and 

 gut microbiome},

author = {Jiafei Wu and Sergio Andreu-Sánchez and Haoran Peng and Ranko Gacesa and Milla Brand ao Gois and Siobhan Brushett and Rinse Weersma and Daoming Wang and Alexander Kurilshikov and Alexandra Zhernakova and Jingyuan Fu and Daria V Zhernakova},

year  = {2026},

date = {2026-02-01},

journal = {Nat. Commun.},

volume = {17},

number = {1},

publisher = {Springer Science and Business Media LLC},

abstract = {Emerging evidence suggests a bidirectional relationship between 

 sleep and the gut microbiome. In this study, we explore the 

 associations of sleep characteristics with lifestyle factors and 

 gut microbiome composition in 6941 participants from the 

 Lifelines Dutch Microbiome Project. We show that lower alpha 

 diversity is associated with poorer sleep quality, later 

 chronotype, and greater social jet lag, while beta diversity is 

 linked to both sleep quality and social jet lag. Of the 137 

 bacterial species associated with sleep, 35.6% are validated in 

 an independent cohort. Mediation analyses indicate that, while 

 changes in species abundance are largely a consequence of sleep 

 behavior, certain species may mediate diet's influence on sleep. 

 For example, we find that Clostridia species UC5_1_1E11 and 

 SGB14844 mediate the effect of coffee intake on social jet lag. 

 These findings highlight the intricate relationship between 

 diet, the gut microbiome, and sleep, suggesting the potential 

 for microbiome-targeted interventions to improve sleep health.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Zhernakova2024-gv,

title = {Host genetic regulation of human gut microbial structural 

 variation},

author = {Daria V Zhernakova and Daoming Wang and Lei Liu and Sergio Andreu-Sánchez and Yue Zhang and Angel J Ruiz-Moreno and Haoran Peng and Niels Plomp and Ángela Del Castillo-Izquierdo and Ranko Gacesa and Esteban A Lopera-Maya and Godfrey S Temba and Vesla I Kullaya and Sander S Leeuwen and Lifelines Cohort Study and Ramnik J Xavier and Quirijn Mast and Leo A B Joosten and Niels P Riksen and Joost H W Rutten and Mihai G Netea and Serena Sanna and Cisca Wijmenga and Rinse K Weersma and Alexandra Zhernakova and Hermie J M Harmsen and Jingyuan Fu},

year  = {2024},

date = {2024-01-01},

journal = {Nature},

volume = {625},

number = {7996},

pages = {813--821},

publisher = {Springer Science and Business Media LLC},

abstract = {Älthough the impact of host genetics on gut microbial diversity 

 and the abundance of specific taxa is well established1-6, 

 little is known about how host genetics regulates the genetic 

 diversity of gut microorganisms. Here we conducted a 

 meta-analysis of associations between human genetic variation 

 and gut microbial structural variation in 9,015 individuals from 

 four Dutch cohorts. Strikingly, the presence rate of a 

 structural variation segment in Faecalibacterium prausnitzii 

 that harbours an N-acetylgalactosamine (GalNAc) utilization gene 

 cluster is higher in individuals who secrete the type A 

 oligosaccharide antigen terminating in GalNAc, a feature that is 

 jointly determined by human ABO and FUT2 genotypes, and we could 

 replicate this association in a Tanzanian cohort. In vitro 

 experiments demonstrated that GalNAc can be used as the sole 

 carbohydrate source for F. prausnitzii strains that carry the 

 GalNAc-metabolizing pathway. Further in silico and in vitro 

 studies demonstrated that other ABO-associated species can also 

 utilize GalNAc, particularly Collinsella aerofaciens. The GalNAc 

 utilization genes are also associated with the host's 

 cardiometabolic health, particularly in individuals with mucosal 

 A-antigen. Together, the findings of our study demonstrate that 

 genetic associations across the human genome and bacterial 

 metagenome can provide functional insights into the reciprocal 

 host-microbiome relationship."},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Chen2022-am,

title = {Influence of the microbiome, diet and genetics on 

 inter-individual variation in the human plasma metabolome},

author = {Lianmin Chen and Daria V Zhernakova and Alexander Kurilshikov and Sergio Andreu-Sánchez and Daoming Wang and Hannah E Augustijn and Arnau Vich Vila and Lifelines Cohort Study and Rinse K Weersma and Marnix H Medema and Mihai G Netea and Folkert Kuipers and Cisca Wijmenga and Alexandra Zhernakova and Jingyuan Fu},

year  = {2022},

date = {2022-11-01},

journal = {Nat. Med.},

volume = {28},

number = {11},

pages = {2333--2343},

publisher = {Springer Science and Business Media LLC},

abstract = {The levels of the thousands of metabolites in the human plasma 

 metabolome are strongly influenced by an individual's genetics 

 and the composition of their diet and gut microbiome. Here, by 

 assessing 1,183 plasma metabolites in 1,368 extensively 

 phenotyped individuals from the Lifelines DEEP and Genome of the 

 Netherlands cohorts, we quantified the proportion of 

 inter-individual variation in the plasma metabolome explained by 

 different factors, characterizing 610, 85 and 38 metabolites as 

 dominantly associated with diet, the gut microbiome and 

 genetics, respectively. Moreover, a diet quality score derived 

 from metabolite levels was significantly associated with diet 

 quality, as assessed by a detailed food frequency questionnaire. 

 Through Mendelian randomization and mediation analyses, we 

 revealed putative causal relationships between diet, the gut 

 microbiome and metabolites. For example, Mendelian randomization 

 analyses support a potential causal effect of Eubacterium 

 rectale in decreasing plasma levels of hydrogen sulfite-a toxin 

 that affects cardiovascular function. Lastly, based on analysis 

 of the plasma metabolome of 311 individuals at two time points 

 separated by 4 years, we observed a positive correlation between 

 the stability of metabolite levels and the amount of variance in 

 the levels of that metabolite that could be explained in our 

 analysis. Altogether, characterization of factors that explain 

 inter-individual variation in the plasma metabolome can help 

 design approaches for modulating diet or the gut microbiome to 

 shape a healthy metabolome.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Zhernakova2022-av,

title = {Age-dependent sex differences in cardiometabolic risk factors},

author = {Daria V Zhernakova and Trishla Sinha and Sergio Andreu-Sánchez and Jelmer R Prins and Alexander Kurilshikov and Jan-Willem Balder and Serena Sanna and Lifelines Cohort Study and Lude Franke and Jan A Kuivenhoven and Alexandra Zhernakova and Jingyuan Fu},

year  = {2022},

date = {2022-09-01},

urldate = {2022-09-01},

journal = {Nat. Cardiovasc. Res.},

volume = {1},

number = {9},

pages = {844--854},

publisher = {Springer Science and Business Media LLC},

abstract = {Cardiometabolic diseases (CMDs) are a major cause of mortality 

 worldwide, yet men and women present remarkable differences in 

 disease prognosis, onset and manifestation. Here we characterize 

 how sex differences in cardiometabolic risk factors vary with 

 age by examining 45 phenotypes and 6 lifestyle factors in 

 146,021 participants of the Dutch population cohort Lifelines. 

 We show that sex differences are present in 71% of the studied 

 phenotypes. For 31% of these phenotypes, the phenotypic 

 difference between sexes is dependent on age. CMD risk factors 

 show various patterns of age-related sex differences, ranging 

 from no difference for phenotypes such as body mass index (BMI) 

 to strong age-modified sex differences for lipid levels. We also 

 identify lifestyle factors that influence phenotypes in a sex- 

 and age-dependent manner. These results highlight the importance 

 of taking age into account when studying sex differences in 

 CMDs.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Kurilshikov2021-sr,

title = {Large-scale association analyses identify host factors 

 influencing human gut microbiome composition},

author = {Alexander Kurilshikov and Carolina Medina-Gomez and Rodrigo Bacigalupe and Djawad Radjabzadeh and Jun Wang and Ayse Demirkan and Caroline I Le Roy and Juan Antonio Raygoza Garay and Casey T Finnicum and Xingrong Liu and Daria V Zhernakova and Marc Jan Bonder and Tue H Hansen and Fabian Frost and Malte C Rühlemann and Williams Turpin and Jee-Young Moon and Han-Na Kim and Kreete Lüll and Elad Barkan and Shiraz A Shah and Myriam Fornage and Joanna Szopinska-Tokov and Zachary D Wallen and Dmitrii Borisevich and Lars Agreus and Anna Andreasson and Corinna Bang and Larbi Bedrani and Jordana T Bell and Hans Bisgaard and Michael Boehnke and Dorret I Boomsma and Robert D Burk and Annique Claringbould and Kenneth Croitoru and Gareth E Davies and Cornelia M Duijn and Liesbeth Duijts and Gwen Falony and Jingyuan Fu and Adriaan Graaf and Torben Hansen and Georg Homuth and David A Hughes and Richard G Ijzerman and Matthew A Jackson and Vincent W V Jaddoe and Marie Joossens and Torben Jørgensen and Daniel Keszthelyi and Rob Knight and Markku Laakso and Matthias Laudes and Lenore J Launer and Wolfgang Lieb and Aldons J Lusis and Ad A M Masclee and Henriette A Moll and Zlatan Mujagic and Qi Qibin and Daphna Rothschild and Hocheol Shin and Søren J Sørensen and Claire J Steves and Jonathan Thorsen and Nicholas J Timpson and Raul Y Tito and Sara Vieira-Silva and Uwe Völker and Henry Völzke and Urmo V osa and Kaitlin H Wade and Susanna Walter and Kyoko Watanabe and Stefan Weiss and Frank U Weiss and Omer Weissbrod and Harm-Jan Westra and Gonneke Willemsen and Haydeh Payami and Daisy M A E Jonkers and Alejandro Arias Vasquez and Eco J C Geus and Katie A Meyer and Jakob Stokholm and Eran Segal and Elin Org and Cisca Wijmenga and Hyung-Lae Kim and Robert C Kaplan and Tim D Spector and Andre G Uitterlinden and Fernando Rivadeneira and Andre Franke and Markus M Lerch and Lude Franke and Serena Sanna and Mauro DÁmato and Oluf Pedersen and Andrew D Paterson and Robert Kraaij and Jeroen Raes and Alexandra Zhernakova},

year  = {2021},

date = {2021-02-01},

journal = {Nat. Genet.},

volume = {53},

number = {2},

pages = {156--165},

publisher = {Springer Science and Business Media LLC},

abstract = {To study the effect of host genetics on gut microbiome 

 composition, the MiBioGen consortium curated and analyzed 

 genome-wide genotypes and 16S fecal microbiome data from 18,340 

 individuals (24 cohorts). Microbial composition showed high 

 variability across cohorts: only 9 of 410 genera were detected 

 in more than 95% of samples. A genome-wide association study of 

 host genetic variation regarding microbial taxa identified 31 

 loci affecting the microbiome at a genome-wide significant (P < 

 5 $times$ 10-8) threshold. One locus, the lactase (LCT) gene 

 locus, reached study-wide significance (genome-wide association study signal: P = 1.28 $times$ 10-20), and it showed an 

 age-dependent association with Bifidobacterium abundance. Other 

 associations were suggestive (1.95 $times$ 10-10 < P < 5 

 $times$ 10-8) but enriched for taxa showing high heritability 

 and for genes expressed in the intestine and brain. A 

 phenome-wide association study and Mendelian randomization 

 identified enrichment of microbiome trait loci in the metabolic, 

 nutrition and environment domains and suggested the microbiome 

 might have causal effects in ulcerative colitis and rheumatoid 

 arthritis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Zhernakova2020-vk,

title = {Genome-wide sequence analyses of ethnic populations across 

 Russia},

author = {Daria V Zhernakova and Vladimir Brukhin and Sergey Malov and Taras K Oleksyk and Klaus Peter Koepfli and Anna Zhuk and Pavel Dobrynin and Sergei Kliver and Nikolay Cherkasov and Gaik Tamazian and Mikhail Rotkevich and Ksenia Krasheninnikova and Igor Evsyukov and Sviatoslav Sidorov and Anna Gorbunova and Ekaterina Chernyaeva and Andrey Shevchenko and Sofia Kolchanova and Alexei Komissarov and Serguei Simonov and Alexey Antonik and Anton Logachev and Dmitrii E Polev and Olga A Pavlova and Andrey S Glotov and Vladimir Ulantsev and Ekaterina Noskova and Tatyana K Davydova and Tatyana M Sivtseva and Svetlana Limborska and Oleg Balanovsky and Vladimir Osakovsky and Alexey Novozhilov and Valery Puzyrev and Stephen J O'Brien},

year  = {2020},

date = {2020-01-01},

journal = {Genomics},

volume = {112},

number = {1},

pages = {442--458},

publisher = {Elsevier BV},

abstract = {The Russian Federation is the largest and one of the most 

 ethnically diverse countries in the world, however no 

 centralized reference database of genetic variation exists to 

 date. Such data are crucial for medical genetics and essential 

 for studying population history. The Genome Russia Project aims 

 at filling this gap by performing whole genome sequencing and 

 analysis of peoples of the Russian Federation. Here we report 

 the characterization of genome-wide variation of 264 healthy 

 adults, including 60 newly sequenced samples. People of Russia 

 carry known and novel genetic variants of adaptive, clinical and 

 functional consequence that in many cases show allele frequency 

 divergence from neighboring populations. Population genetics 

 analyses revealed six phylogeographic partitions among 

 indigenous ethnicities corresponding to their geographic 

 locales. This study presents a characterization of 

 population-specific genomic variation in Russia with results 

 important for medical genetics and for understanding the dynamic 

 population history of the world's largest country.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Zhernakova2018-wt,

title = {Individual variations in cardiovascular-disease-related protein 

 levels are driven by genetics and gut microbiome},

author = {Daria V Zhernakova and Trang H Le and Alexander Kurilshikov and Biljana Atanasovska and Marc Jan Bonder and Serena Sanna and Annique Claringbould and Urmo V osa and Patrick Deelen and Lude Franke and Rudolf A Boer and Folkert Kuipers and Mihai G Netea and Marten H Hofker and Cisca Wijmenga and Alexandra Zhernakova and Jingyuan Fu and LifeLines study and BIOS consortium},

year  = {2018},

date = {2018-11-01},

journal = {Nat. Genet.},

volume = {50},

number = {11},

pages = {1524--1532},

publisher = {Springer Science and Business Media LLC},

abstract = {Despite a growing body of evidence, the role of the gut 

 microbiome in cardiovascular diseases is still unclear. Here, we 

 present a systems-genome-wide and metagenome-wide association 

 study on plasma concentrations of 92 

 cardiovascular-disease-related proteins in the population cohort 

 LifeLines-DEEP. We identified genetic components for 73 proteins 

 and microbial associations for 41 proteins, of which 31 were 

 associated to both. The genetic and microbial factors identified 

 mostly exert additive effects and collectively explain up to 

 76.6% of inter-individual variation (17.5% on average). 

 Genetics contribute most to concentrations of immune-related 

 proteins, while the gut microbiome contributes most to proteins 

 involved in metabolism and intestinal health. We found several 

 host-microbe interactions that impact proteins involved in 

 epithelial function, lipid metabolism, and central nervous 

 system function. This study provides important evidence for a 

 joint genetic and microbial effect in cardiovascular disease and 

 provides directions for future applications in personalized 

 medicine.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Zhernakova2017-gc,

title = {Identification of context-dependent expression quantitative 

 trait loci in whole blood},

author = {Daria V Zhernakova and Patrick Deelen and Martijn Vermaat and Maarten Iterson and Michiel Galen and Wibowo Arindrarto and Peter Hof and Hailiang Mei and Freerk Dijk and Harm-Jan Westra and Marc Jan Bonder and Jeroen Rooij and Marijn Verkerk and P Mila Jhamai and Matthijs Moed and Szymon M Kielbasa and Jan Bot and Irene Nooren and René Pool and Jenny Dongen and Jouke J Hottenga and Coen D A Stehouwer and Carla J H Kallen and Casper G Schalkwijk and Alexandra Zhernakova and Yang Li and Ettje F Tigchelaar and Niek Klein and Marian Beekman and Joris Deelen and Diana Heemst and Leonard H Berg and Albert Hofman and André G Uitterlinden and Marleen M J Greevenbroek and Jan H Veldink and Dorret I Boomsma and Cornelia M Duijn and Cisca Wijmenga and P Eline Slagboom and Morris A Swertz and Aaron Isaacs and Joyce B J Meurs and Rick Jansen and Bastiaan T Heijmans and Peter A C Hoen and Lude Franke},

year  = {2017},

date = {2017-01-01},

journal = {Nat. Genet.},

volume = {49},

number = {1},

pages = {139--145},

publisher = {Springer Science and Business Media LLC},

abstract = {Genetic risk factors often localize to noncoding regions of the 

 genome with unknown effects on disease etiology. Expression 

 quantitative trait loci (eQTLs) help to explain the regulatory 

 mechanisms underlying these genetic associations. Knowledge of 

 the context that determines the nature and strength of eQTLs may 

 help identify cell types relevant to pathophysiology and the 

 regulatory networks underlying disease. Here we generated 

 peripheral blood RNA-seq data from 2,116 unrelated individuals 

 and systematically identified context-dependent eQTLs using a 

 hypothesis-free strategy that does not require previous 

 knowledge of the identity of the modifiers. Of the 23,060 

 significant cis-regulated genes (false discovery rate (FDR) 

 $łeq$ 0.05), 2,743 (12%) showed context-dependent eQTL 

 effects. The majority of these effects were influenced by cell 

 type composition. A set of 145 cis-eQTLs depended on type I 

 interferon signaling. Others were modulated by specific 

 transcription factors binding to the eQTL SNPs.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}