Risk factors

  • Article
    | Open Access

    Prostate cancer progression may be enhanced by a high-fat diet. Here the authors show that a diet high in saturated fats enhance the MYC-driven transcriptional program, a feature that independently predicts prostate cancer progression and death.

    • David P. Labbé
    • , Giorgia Zadra
    • , Meng Yang
    • , Jaime M. Reyes
    • , Charles Y. Lin
    • , Stefano Cacciatore
    • , Ericka M. Ebot
    • , Amanda L. Creech
    • , Francesca Giunchi
    • , Michelangelo Fiorentino
    • , Habiba Elfandy
    • , Sudeepa Syamala
    • , Edward D. Karoly
    • , Mohammed Alshalalfa
    • , Nicholas Erho
    • , Ashley Ross
    • , Edward M. Schaeffer
    • , Ewan A. Gibb
    • , Mandeep Takhar
    • , Robert B. Den
    • , Jonathan Lehrer
    • , R. Jeffrey Karnes
    • , Stephen J. Freedland
    • , Elai Davicioni
    • , Daniel E. Spratt
    • , Leigh Ellis
    • , Jacob D. Jaffe
    • , Anthony V. DʼAmico
    • , Philip W. Kantoff
    • , James E. Bradner
    • , Lorelei A. Mucci
    • , Jorge E. Chavarro
    • , Massimo Loda
    •  & Myles Brown
  • Article
    | Open Access

    Here, Shah et al. perform a meta-analysis and show that people who live or work in agricultural land in Southeast Asia are on average 1.7 times more likely to be infected with a pathogen than controls, suggesting that agricultural land-use increases infectious disease risk.

    • Hiral A. Shah
    • , Paul Huxley
    • , Jocelyn Elmes
    •  & Kris A. Murray
  • Article
    | Open Access

    Here, Williamson et al. combine epidemiological and genomic analysis of 2,186 Neisseria gonorrhoeae isolates from Australia and show that men who have sex with men and women are a possible ‘bridging’ population between men who have sex with men and heterosexuals.

    • Deborah A. Williamson
    • , Eric P. F. Chow
    • , Claire L. Gorrie
    • , Torsten Seemann
    • , Danielle J. Ingle
    • , Nasra Higgins
    • , Marion Easton
    • , George Taiaroa
    • , Yonatan H. Grad
    • , Jason C. Kwong
    • , Christopher K. Fairley
    • , Marcus Y. Chen
    •  & Benjamin P. Howden
  • Article
    | Open Access

    Air pollution has become a major health risk in China. Here Zhang et al. report that maternal and neonatal exposure to particulate matter increases the risk of neonatal jaundice based on the study of 25,782 newborns born in China between 2014 and 2017.

    • Liqiang Zhang
    • , Weiwei Liu
    • , Kun Hou
    • , Jintai Lin
    • , Changqing Song
    • , Chenghu Zhou
    • , Bo Huang
    • , Xiaohua Tong
    • , Jinfeng Wang
    • , William Rhine
    • , Ying Jiao
    • , Ziwei Wang
    • , Ruijing Ni
    • , Mengyao Liu
    • , Liang Zhang
    • , Ziye Wang
    • , Yuebin Wang
    • , Xingang Li
    • , Suhong Liu
    •  & Yanhong Wang
  • Article
    | Open Access

    Genome-wide association studies have only revealed a handful of genetic loci for longevity. Here, in a case–control design based on phenotype definitions of individuals surviving at or beyond the age corresponding to the 90th and 99th survival percentile, the authors report two additional loci located in the APOE locus and near GPR78.

    • Joris Deelen
    • , Daniel S. Evans
    • , Dan E. Arking
    • , Niccolò Tesi
    • , Marianne Nygaard
    • , Xiaomin Liu
    • , Mary K. Wojczynski
    • , Mary L. Biggs
    • , Ashley van der Spek
    • , Gil Atzmon
    • , Erin B. Ware
    • , Chloé Sarnowski
    • , Albert V. Smith
    • , Ilkka Seppälä
    • , Heather J. Cordell
    • , Janina Dose
    • , Najaf Amin
    • , Alice M. Arnold
    • , Kristin L. Ayers
    • , Nir Barzilai
    • , Elizabeth J. Becker
    • , Marian Beekman
    • , Hélène Blanché
    • , Kaare Christensen
    • , Lene Christiansen
    • , Joanna C. Collerton
    • , Sarah Cubaynes
    • , Steven R. Cummings
    • , Karen Davies
    • , Birgit Debrabant
    • , Jean-François Deleuze
    • , Rachel Duncan
    • , Jessica D. Faul
    • , Claudio Franceschi
    • , Pilar Galan
    • , Vilmundur Gudnason
    • , Tamara B. Harris
    • , Martijn Huisman
    • , Mikko A. Hurme
    • , Carol Jagger
    • , Iris Jansen
    • , Marja Jylhä
    • , Mika Kähönen
    • , David Karasik
    • , Sharon L. R. Kardia
    • , Andrew Kingston
    • , Thomas B. L. Kirkwood
    • , Lenore J. Launer
    • , Terho Lehtimäki
    • , Wolfgang Lieb
    • , Leo-Pekka Lyytikäinen
    • , Carmen Martin-Ruiz
    • , Junxia Min
    • , Almut Nebel
    • , Anne B. Newman
    • , Chao Nie
    • , Ellen A. Nohr
    • , Eric S. Orwoll
    • , Thomas T. Perls
    • , Michael A. Province
    • , Bruce M. Psaty
    • , Olli T. Raitakari
    • , Marcel J. T. Reinders
    • , Jean-Marie Robine
    • , Jerome I. Rotter
    • , Paola Sebastiani
    • , Jennifer Smith
    • , Thorkild I. A. Sørensen
    • , Kent D. Taylor
    • , André G. Uitterlinden
    • , Wiesje van der Flier
    • , Sven J. van der Lee
    • , Cornelia M. van Duijn
    • , Diana van Heemst
    • , James W. Vaupel
    • , David Weir
    • , Kenny Ye
    • , Yi Zeng
    • , Wanlin Zheng
    • , Henne Holstege
    • , Douglas P. Kiel
    • , Kathryn L. Lunetta
    • , P. Eline Slagboom
    •  & Joanne M. Murabito
  • Article
    | Open Access

    Levels of sodium and potassium in urine are associated with cardiovascular traits. Here, Pazoki et al. perform genome-wide association studies for urinary sodium and potassium secretion and identify 50 and 13 novel loci, respectively, some of which show a potential causal relationship with blood pressure based on MR analysis.

    • Raha Pazoki
    • , Evangelos Evangelou
    • , David Mosen-Ansorena
    • , Rui Climaco Pinto
    • , Ibrahim Karaman
    • , Paul Blakeley
    • , Dipender Gill
    • , Verena Zuber
    • , Paul Elliott
    • , Ioanna Tzoulaki
    •  & Abbas Dehghan
  • Article
    | Open Access

    HLA alleles and microbiome alterations have been separately associated with human autoimmunity. Here the authors identify differences in stool microbiome between healthy carriers of HLA alleles conferring low- and high-risk for type 1 diabetes, suggesting that HLA shaping of microbiome may contribute to HLA impact on autoimmunity risks.

    • Jordan T. Russell
    • , Luiz F. W. Roesch
    • , Malin Ördberg
    • , Jorma Ilonen
    • , Mark A. Atkinson
    • , Desmond A. Schatz
    • , Eric W. Triplett
    •  & Johnny Ludvigsson
  • Article
    | Open Access

    Heatwaves are expected to increase under climate change, and so are the associated deaths. Here the authors determine the regional high temperature thresholds for 27 metropolises in China and analyze the changes to heat-related mortality, showing that the additional global-warming temperature increase of 0.5°C, from 1.5°C to 2.0°C, will lead to tens of thousands of additional deaths, annually.

    • Yanjun Wang
    • , Anqian Wang
    • , Jianqing Zhai
    • , Hui Tao
    • , Tong Jiang
    • , Buda Su
    • , Jun Yang
    • , Guojie Wang
    • , Qiyong Liu
    • , Chao Gao
    • , Zbigniew W. Kundzewicz
    • , Mingjin Zhan
    • , Zhiqiang Feng
    •  & Thomas Fischer
  • Article
    | Open Access

    Predominant participation of European-ancestry individuals in genetic studies has hindered the better understanding of genetic risk in non-European ancestry individuals. Here, Duncan et al. quantify polygenic risk score use and performance in worldwide populations.

    • L. Duncan
    • , H. Shen
    • , B. Gelaye
    • , J. Meijsen
    • , K. Ressler
    • , M. Feldman
    • , R. Peterson
    •  & B. Domingue
  • Article
    | Open Access

    Here, Elovitz et al. investigate associations between cervicovaginal microbiota (CVM) and spontaneous preterm birth (sPTB) in a large cohort of African American and non-African American women, and find that CVM and local immune response early in pregnancy are associated with sPTB in an ethnicity-dependent manner.

    • Michal A. Elovitz
    • , Pawel Gajer
    • , Valerie Riis
    • , Amy G. Brown
    • , Michael S. Humphrys
    • , Johanna B. Holm
    •  & Jacques Ravel
  • Article
    | Open Access

    Lack of knowledge of individual infection history hinders understanding of immunological interactions among DENV serotypes. Here, the authors introduce a framework to infer the relationship between unobserved infection history and subsequent infection and disease risk, and find complex dependencies.

    • Tim K. Tsang
    • , Samson L. Ghebremariam
    • , Lionel Gresh
    • , Aubree Gordon
    • , M. Elizabeth Halloran
    • , Leah C. Katzelnick
    • , Diana Patricia Rojas
    • , Guillermina Kuan
    • , Angel Balmaseda
    • , Jonathan Sugimoto
    • , Eva Harris
    • , Ira M. Longini Jr.
    •  & Yang Yang
  • Review Article
    | Open Access

    How can scientists and policymakers work together to reduce the health impacts of air pollution? In this review paper, the authors discuss the interplay between advances in environmental exposure assessment and policy advances to tackle pollution in a focused way.

    • Andrew Caplin
    • , Masoud Ghandehari
    • , Chris Lim
    • , Paul Glimcher
    •  & George Thurston
  • Article
    | Open Access

    Sleep is essential for homeostasis and insufficient or excessive sleep are associated with adverse outcomes. Here, the authors perform GWAS for self-reported habitual sleep duration in adults, supported by accelerometer-derived measures, and identify genetic correlation with psychiatric and metabolic traits

    • Hassan S. Dashti
    • , Samuel E. Jones
    • , Andrew R. Wood
    • , Jacqueline M. Lane
    • , Vincent T. van Hees
    • , Heming Wang
    • , Jessica A. Rhodes
    • , Yanwei Song
    • , Krunal Patel
    • , Simon G. Anderson
    • , Robin N. Beaumont
    • , David A. Bechtold
    • , Jack Bowden
    • , Brian E. Cade
    • , Marta Garaulet
    • , Simon D. Kyle
    • , Max A. Little
    • , Andrew S. Loudon
    • , Annemarie I. Luik
    • , Frank A. J. L. Scheer
    • , Kai Spiegelhalder
    • , Jessica Tyrrell
    • , Daniel J. Gottlieb
    • , Henning Tiemeier
    • , David W. Ray
    • , Shaun M. Purcell
    • , Timothy M. Frayling
    • , Susan Redline
    • , Deborah A. Lawlor
    • , Martin K. Rutter
    • , Michael N. Weedon
    •  & Richa Saxena
  • Article
    | Open Access

    Here, the authors explore the relationship between socioeconomic position (SEP) across the life course and inflammation in a multi-cohort study and show that educational attainment is most strongly related to inflammation, suggesting that socioeconomic disadvantage in young adulthood is independently associated with later life inflammation.

    • Eloïse Berger
    • , Raphaële Castagné
    • , Marc Chadeau-Hyam
    • , Murielle Bochud
    • , Angelo d’Errico
    • , Martina Gandini
    • , Maryam Karimi
    • , Mika Kivimäki
    • , Vittorio Krogh
    • , Michael Marmot
    • , Salvatore Panico
    • , Martin Preisig
    • , Fulvio Ricceri
    • , Carlotta Sacerdote
    • , Andrew Steptoe
    • , Silvia Stringhini
    • , Rosario Tumino
    • , Paolo Vineis
    • , Cyrille Delpierre
    •  & Michelle Kelly-Irving
  • Article
    | Open Access

    While human lifespan is only moderately heritable, “getting old” runs in families. Here, van den Berg et al. study mortality data from three-generation cohorts to define a threshold for longevity and find that individuals have an increasing survival advantage with each additional relative in the top 10% survivors of their birth cohort.

    • Niels van den Berg
    • , Mar Rodríguez-Girondo
    • , Ingrid K. van Dijk
    • , Rick J. Mourits
    • , Kees Mandemakers
    • , Angelique A. P. O. Janssens
    • , Marian Beekman
    • , Ken R. Smith
    •  & P. Eline Slagboom
  • Article
    | Open Access

    Acne vulgaris is a chronic inflammation of the skin, the genetic basis of which is incompletely understood. Here, Petridis et al. perform GWAS and meta-analysis for acne in 26,722 individuals and identify 12 novel risk loci that implicate structure and maintenance of the skin in severe acne risk.

    • Christos Petridis
    • , Alexander A. Navarini
    • , Nick Dand
    • , Jake Saklatvala
    • , David Baudry
    • , Michael Duckworth
    • , Michael H. Allen
    • , Charles J. Curtis
    • , Sang Hyuck Lee
    • , A. David Burden
    • , Alison Layton
    • , Veronique Bataille
    • , Andrew E. Pink
    • , Anton Alexandroff
    • , Alex Anstey
    • , Jaskiran Azad
    • , Omar Aziz
    • , Nigel Burrows
    • , Aamir Butt
    • , Peter Cartwright
    • , Anna Chapman
    • , Timothy H. Clayton
    • , Sandeep Cliff
    • , Tim Cutler
    • , Brigid Daly
    • , Amrit Darvay
    • , Claudia DeGiovanni
    • , Anthony Downs
    • , Colm Dwyer
    • , John English
    • , Adam Ferguson
    • , Colin Fleming
    • , Elizabeth Fraser-Andrews
    • , Mark Goodfield
    • , Clive E. Grattan
    • , Hartmut Hempel
    • , Sue Hood
    • , Bronwyn Hughes
    • , Evmorfia Ladoyanni
    • , Calum Lyon
    • , Ali Mahmud
    • , Moshin Malik
    • , Eleanor Mallon
    • , Simon Meggitt
    • , Andrew Messenger
    • , Yaaseen Moosa
    • , Stephanie Munn
    • , Anthony Ormerod
    • , Deepak Rallan
    • , Janet Ross
    • , Ingrid Salvary
    • , Rachel Wachsmuth
    • , Shyamal Wahie
    • , Shernaz Walton
    • , Sarah Walsh
    • , Diane Williamson
    • , Carolyn Willis
    • , Isabelle Carlavan
    • , Johannes J. Voegel
    • , Timothy D. Spector
    • , Richard C. Trembath
    • , John A. McGrath
    • , Catherine H. Smith
    • , Jonathan N. Barker
    •  & Michael A. Simpson
  • Article
    | Open Access

    Nutritional experience can have phenotypic consequences in subsequent generations, as is evident from studies in animals and plants. Here, Vågerö et al. find in a large three-generation cohort that access to food in the paternal grandfather associates with all-cause and cancer mortality in male grandchildren.

    • Denny Vågerö
    • , Pia R. Pinger
    • , Vanda Aronsson
    •  & Gerard J. van den Berg
  • Article
    | Open Access

    Local air quality co-benefits can provide convincing support for climate action. Here the authors revisited air quality co-benefits of climate action in the context of NDCs and found that 71–99 thousand premature deaths can be avoided each year by 2030, offsetting the climate mitigation costs on a global level.

    • Toon Vandyck
    • , Kimon Keramidas
    • , Alban Kitous
    • , Joseph V. Spadaro
    • , Rita Van Dingenen
    • , Mike Holland
    •  & Bert Saveyn
  • Article
    | Open Access

    Infants born to obese mothers have altered microbiome and increased risk of obesity and NAFLD. Here the authors establish causality by showing that maternal obesity-shaped infant gut microbiome induces macrophage dysfunction, inflammation, and diet-induced metabolic disease in germ-free mice.

    • Taylor K. Soderborg
    • , Sarah E. Clark
    • , Christopher E. Mulligan
    • , Rachel C. Janssen
    • , Lyndsey Babcock
    • , Diana Ir
    • , Bridget Young
    • , Nancy Krebs
    • , Dominick J. Lemas
    • , Linda K. Johnson
    • , Tiffany Weir
    • , Laurel L. Lenz
    • , Daniel N. Frank
    • , Teri L. Hernandez
    • , Kristine A. Kuhn
    • , Angelo D’Alessandro
    • , Linda A. Barbour
    • , Karim C. El Kasmi
    •  & Jacob E. Friedman
  • Article
    | Open Access

    Elevated serum urate levels are a risk factor for gout. Here, Tin et al. perform whole-exome sequencing in 19,517 individuals and detect low-frequency genetic variants in urate transporter genes, SLC22A12 and SLC2A9, associated with serum urate levels and confirm their damaging nature in vitro and in silico.

    • Adrienne Tin
    • , Yong Li
    • , Jennifer A. Brody
    • , Teresa Nutile
    • , Audrey Y. Chu
    • , Jennifer E. Huffman
    • , Qiong Yang
    • , Ming-Huei Chen
    • , Cassianne Robinson-Cohen
    • , Aurélien Macé
    • , Jun Liu
    • , Ayşe Demirkan
    • , Rossella Sorice
    • , Sanaz Sedaghat
    • , Melody Swen
    • , Bing Yu
    • , Sahar Ghasemi
    • , Alexanda Teumer
    • , Peter Vollenweider
    • , Marina Ciullo
    • , Meng Li
    • , André G. Uitterlinden
    • , Robert Kraaij
    • , Najaf Amin
    • , Jeroen van Rooij
    • , Zoltán Kutalik
    • , Abbas Dehghan
    • , Barbara McKnight
    • , Cornelia M. van Duijn
    • , Alanna Morrison
    • , Bruce M. Psaty
    • , Eric Boerwinkle
    • , Caroline S. Fox
    • , Owen M. Woodward
    •  & Anna Köttgen
  • Article
    | Open Access

    IL-1β in gingival crevicular fluid (GCF) is a marker of inflammation in periodontal disease. Here, Offenbacher et al. identify genetic variants in the IL37 locus associated with GCF-IL-1β and show that the IL-1β-increasing allele at rs3811046 leads to an enhanced inflammatory response in vitro and in vivo.

    • Steven Offenbacher
    • , Yizu Jiao
    • , Steven J. Kim
    • , Julie Marchesan
    • , Kevin L. Moss
    • , Li Jing
    • , Kimon Divaris
    • , Sompop Bencharit
    • , Cary S. Agler
    • , Thiago Morelli
    • , Shaoping Zhang
    • , Lu Sun
    • , William T. Seaman
    • , Dale Cowley
    • , Silvana P. Barros
    • , James D. Beck
    • , Matthias Munz
    • , Arne S. Schaefer
    •  & Kari E. North
  • Article
    | Open Access

    Biomarker identification requires prohibitively large cohorts with gene expression and phenotype data. The approach introduced here learns polygenic predictors of expression from genetic and expression data, used to infer biomarker levels in patients with genetic and disease information.

    • Jonathan D. Mosley
    • , QiPing Feng
    • , Quinn S. Wells
    • , Sara L. Van Driest
    • , Christian M. Shaffer
    • , Todd L. Edwards
    • , Lisa Bastarache
    • , Wei-Qi Wei
    • , Lea K. Davis
    • , Catherine A. McCarty
    • , Will Thompson
    • , Christopher G. Chute
    • , Gail P. Jarvik
    • , Adam S. Gordon
    • , Melody R. Palmer
    • , David R. Crosslin
    • , Eric B. Larson
    • , David S. Carrell
    • , Iftikhar J. Kullo
    • , Jennifer A. Pacheco
    • , Peggy L. Peissig
    • , Murray H. Brilliant
    • , James G. Linneman
    • , Bahram Namjou
    • , Marc S. Williams
    • , Marylyn D. Ritchie
    • , Kenneth M. Borthwick
    • , Shefali S. Verma
    • , Jason H. Karnes
    • , Scott T. Weiss
    • , Thomas J. Wang
    • , C. Michael Stein
    • , Josh C. Denny
    •  & Dan M. Roden
  • Article
    | Open Access

    This study analyzes allelic expression bias in post-mortem brains of healthy individuals and those diagnosed with schizophrenia or bipolar disorder. The study shows that the number of imprinted genes is consistent with low estimates, and that allelic bias is independent of psychiatric disease status.

    • Attila Gulyás-Kovács
    • , Ifat Keydar
    • , Eva Xia
    • , Menachem Fromer
    • , Gabriel Hoffman
    • , Douglas Ruderfer
    • , Ravi Sachidanandam
    •  & Andrew Chess
  • Article
    | Open Access

    Little is known about the genetic determinants of social isolation and loneliness despite their well-established importance for health. Here, using multi-trait GWAS, Day et al. identify 15 genomic loci for loneliness and further show a bidirectional causal relationship between BMI and loneliness by MR.

    • Felix R. Day
    • , Ken K. Ong
    •  & John R. B. Perry
  • Article
    | Open Access

    Primary open-angle glaucoma (POAG) leads to progressive vision loss. Here, Choquet et al. perform genome-wide association analysis for POAG in a multi-ethnic cohort, identify a total of nine novel genetic loci and show relevant function of FMNL2 and LMX1B using cell line and mouse experiments.

    • Hélène Choquet
    • , Seyyedhassan Paylakhi
    • , Stephen C. Kneeland
    • , Khanh K. Thai
    • , Thomas J. Hoffmann
    • , Jie Yin
    • , Mark N. Kvale
    • , Yambazi Banda
    • , Nicholas G. Tolman
    • , Pete A. Williams
    • , Catherine Schaefer
    • , Ronald B. Melles
    • , Neil Risch
    • , Simon W. M. John
    • , K. Saidas Nair
    •  & Eric Jorgenson
  • Article
    | Open Access

    ELL2 was recently discovered as a susceptibility gene for multiple myeloma (MM). Here, they show that the MM risk allele lowers ELL2 expression in plasma cells, that it also upregulates gene sets related to ribosome biogenesis, and that one of the linked variants reduces binding of MAFF/G/K family transcription factors.

    • Mina Ali
    • , Ram Ajore
    • , Anna-Karin Wihlborg
    • , Abhishek Niroula
    • , Bhairavi Swaminathan
    • , Ellinor Johnsson
    • , Owen W Stephens
    • , Gareth Morgan
    • , Tobias Meissner
    • , Ingemar Turesson
    • , Hartmut Goldschmidt
    • , Ulf-Henrik Mellqvist
    • , Urban Gullberg
    • , Markus Hansson
    • , Kari Hemminki
    • , Hareth Nahi
    • , Anders Waage
    • , Niels Weinhold
    •  & Björn Nilsson
  • Article
    | Open Access

    Childhood acute lymphoblastic leukemia is common in Latino Americans. Here, the authors conduct a genome-wide association study in a Californian cohort containing children of Latino heritage, and identify loci on 17q12 and 8q24 which may affect hematopoietic and growth-regulation pathways.

    • Joseph L. Wiemels
    • , Kyle M. Walsh
    • , Adam J. de Smith
    • , Catherine Metayer
    • , Semira Gonseth
    • , Helen M. Hansen
    • , Stephen S. Francis
    • , Juhi Ojha
    • , Ivan Smirnov
    • , Lisa Barcellos
    • , Xiaorong Xiao
    • , Libby Morimoto
    • , Roberta McKean-Cowdin
    • , Rong Wang
    • , Herbert Yu
    • , Josephine Hoh
    • , Andrew T. DeWan
    •  & Xiaomei Ma
  • Article
    | Open Access

    Vitamin D deficiency is associated with multiple human pathologic conditions. In a genome-wide association study of 79,366 individuals, Jiang et al. replicate four and identify two new genetic loci for serum levels of 25-hydroxyvitamin D and find evidence for a shared genetic basis with autoimmune diseases.

    • Xia Jiang
    • , Paul F. O’Reilly
    • , Hugues Aschard
    • , Yi-Hsiang Hsu
    • , J. Brent Richards
    • , Josée Dupuis
    • , Erik Ingelsson
    • , David Karasik
    • , Stefan Pilz
    • , Diane Berry
    • , Bryan Kestenbaum
    • , Jusheng Zheng
    • , Jianan Luan
    • , Eleni Sofianopoulou
    • , Elizabeth A. Streeten
    • , Demetrius Albanes
    • , Pamela L. Lutsey
    • , Lu Yao
    • , Weihong Tang
    • , Michael J. Econs
    • , Henri Wallaschofski
    • , Henry Völzke
    • , Ang Zhou
    • , Chris Power
    • , Mark I. McCarthy
    • , Erin D. Michos
    • , Eric Boerwinkle
    • , Stephanie J. Weinstein
    • , Neal D. Freedman
    • , Wen-Yi Huang
    • , Natasja M. Van Schoor
    • , Nathalie van der Velde
    • , Lisette C. P. G. M. de Groot
    • , Anke Enneman
    • , L. Adrienne Cupples
    • , Sarah L. Booth
    • , Ramachandran S. Vasan
    • , Ching-Ti Liu
    • , Yanhua Zhou
    • , Samuli Ripatti
    • , Claes Ohlsson
    • , Liesbeth Vandenput
    • , Mattias Lorentzon
    • , Johan G. Eriksson
    • , M. Kyla Shea
    • , Denise K. Houston
    • , Stephen B. Kritchevsky
    • , Yongmei Liu
    • , Kurt K. Lohman
    • , Luigi Ferrucci
    • , Munro Peacock
    • , Christian Gieger
    • , Marian Beekman
    • , Eline Slagboom
    • , Joris Deelen
    • , Diana van Heemst
    • , Marcus E. Kleber
    • , Winfried März
    • , Ian H. de Boer
    • , Alexis C. Wood
    • , Jerome I. Rotter
    • , Stephen S. Rich
    • , Cassianne Robinson-Cohen
    • , Martin den Heijer
    • , Marjo-Riitta Jarvelin
    • , Alana Cavadino
    • , Peter K. Joshi
    • , James F. Wilson
    • , Caroline Hayward
    • , Lars Lind
    • , Karl Michaëlsson
    • , Stella Trompet
    • , M. Carola Zillikens
    • , Andre G. Uitterlinden
    • , Fernando Rivadeneira
    • , Linda Broer
    • , Lina Zgaga
    • , Harry Campbell
    • , Evropi Theodoratou
    • , Susan M. Farrington
    • , Maria Timofeeva
    • , Malcolm G. Dunlop
    • , Ana M. Valdes
    • , Emmi Tikkanen
    • , Terho Lehtimäki
    • , Leo-Pekka Lyytikäinen
    • , Mika Kähönen
    • , Olli T. Raitakari
    • , Vera Mikkilä
    • , M. Arfan Ikram
    • , Naveed Sattar
    • , J. Wouter Jukema
    • , Nicholas J. Wareham
    • , Claudia Langenberg
    • , Nita G. Forouhi
    • , Thomas E. Gundersen
    • , Kay-Tee Khaw
    • , Adam S. Butterworth
    • , John Danesh
    • , Timothy Spector
    • , Thomas J. Wang
    • , Elina Hyppönen
    • , Peter Kraft
    •  & Douglas P. Kiel
  • Article
    | Open Access

    Genetic methods are useful to test whether risk factors are causal for or consequence of disease. Here, Zhu et al. develop a generalized summary-based Mendelian Randomization (GSMR) method which uses summary-level data from GWAS to test for causal associations of health risk factors with common diseases.

    • Zhihong Zhu
    • , Zhili Zheng
    • , Futao Zhang
    • , Yang Wu
    • , Maciej Trzaskowski
    • , Robert Maier
    • , Matthew R. Robinson
    • , John J. McGrath
    • , Peter M. Visscher
    • , Naomi R. Wray
    •  & Jian Yang
  • Article
    | Open Access

    Intraocular pressure (IOP) is a major risk factor for glaucoma. Here, Choquet and co-authors perform a multi-ethnic genome-wide association study of repeat IOP measurements in 69,756 individuals and identify 40 novel loci, 36 of which show directionally consistent effects in glaucoma.

    • Hélène Choquet
    • , Khanh K. Thai
    • , Jie Yin
    • , Thomas J. Hoffmann
    • , Mark N. Kvale
    • , Yambazi Banda
    • , Catherine Schaefer
    • , Neil Risch
    • , K. Saidas Nair
    • , Ronald Melles
    •  & Eric Jorgenson
  • Article
    | Open Access

    The influence of insulin on food preference and the corresponding underlying neural circuits are unknown in humans. Here, the authors show that increasing insulin changes food preference by modulating mesolimbic neural circuits, and that this pattern is changed in insulin-resistant individuals.

    • Lena J. Tiedemann
    • , Sebastian M. Schmid
    • , Judith Hettel
    • , Katrin Giesen
    • , Paul Francke
    • , Christian Büchel
    •  & Stefanie Brassen
  • Article
    | Open Access

    Heart rate variability (HRV) describes the individual variation in cardiac cycle duration and is a measure of vagal control of heart rate. Here, the authors identify seventeen single-nucleotide polymorphisms associated with HRV, lending new insight into the vagal regulation of heart rhythm.

    • Ilja M. Nolte
    • , M. Loretto Munoz
    • , Vinicius Tragante
    • , Azmeraw T. Amare
    • , Rick Jansen
    • , Ahmad Vaez
    • , Benedikt von der Heyde
    • , Christy L. Avery
    • , Joshua C. Bis
    • , Bram Dierckx
    • , Jenny van Dongen
    • , Stephanie M. Gogarten
    • , Philippe Goyette
    • , Jussi Hernesniemi
    • , Ville Huikari
    • , Shih-Jen Hwang
    • , Deepali Jaju
    • , Kathleen F. Kerr
    • , Alexander Kluttig
    • , Bouwe P. Krijthe
    • , Jitender Kumar
    • , Sander W. van der Laan
    • , Leo-Pekka Lyytikäinen
    • , Adam X. Maihofer
    • , Arpi Minassian
    • , Peter J. van der Most
    • , Martina Müller-Nurasyid
    • , Michel Nivard
    • , Erika Salvi
    • , James D. Stewart
    • , Julian F. Thayer
    • , Niek Verweij
    • , Andrew Wong
    • , Delilah Zabaneh
    • , Mohammad H. Zafarmand
    • , Abdel Abdellaoui
    • , Sulayma Albarwani
    • , Christine Albert
    • , Alvaro Alonso
    • , Foram Ashar
    • , Juha Auvinen
    • , Tomas Axelsson
    • , Dewleen G. Baker
    • , Paul I. W. de Bakker
    • , Matteo Barcella
    • , Riad Bayoumi
    • , Rob J. Bieringa
    • , Dorret Boomsma
    • , Gabrielle Boucher
    • , Annie R. Britton
    • , Ingrid Christophersen
    • , Andrea Dietrich
    • , George B. Ehret
    • , Patrick T. Ellinor
    • , Markku Eskola
    • , Janine F. Felix
    • , John S. Floras
    • , Oscar H. Franco
    • , Peter Friberg
    • , Maaike G. J. Gademan
    • , Mark A. Geyer
    • , Vilmantas Giedraitis
    • , Catharina A. Hartman
    • , Daiane Hemerich
    • , Albert Hofman
    • , Jouke-Jan Hottenga
    • , Heikki Huikuri
    • , Nina Hutri-Kähönen
    • , Xavier Jouven
    • , Juhani Junttila
    • , Markus Juonala
    • , Antti M. Kiviniemi
    • , Jan A. Kors
    • , Meena Kumari
    • , Tatiana Kuznetsova
    • , Cathy C. Laurie
    • , Joop D. Lefrandt
    • , Yong Li
    • , Yun Li
    • , Duanping Liao
    • , Marian C. Limacher
    • , Henry J. Lin
    • , Cecilia M. Lindgren
    • , Steven A. Lubitz
    • , Anubha Mahajan
    • , Barbara McKnight
    • , Henriette Meyer zu Schwabedissen
    • , Yuri Milaneschi
    • , Nina Mononen
    • , Andrew P. Morris
    • , Mike A. Nalls
    • , Gerjan Navis
    • , Melanie Neijts
    • , Kjell Nikus
    • , Kari E. North
    • , Daniel T. O'Connor
    • , Johan Ormel
    • , Siegfried Perz
    • , Annette Peters
    • , Bruce M. Psaty
    • , Olli T. Raitakari
    • , Victoria B. Risbrough
    • , Moritz F. Sinner
    • , David Siscovick
    • , Johannes H. Smit
    • , Nicholas L. Smith
    • , Elsayed Z. Soliman
    • , Nona Sotoodehnia
    • , Jan A. Staessen
    • , Phyllis K. Stein
    • , Adrienne M. Stilp
    • , Katarzyna Stolarz-Skrzypek
    • , Konstantin Strauch
    • , Johan Sundström
    • , Cees A. Swenne
    • , Ann-Christine Syvänen
    • , Jean-Claude Tardif
    • , Kent D. Taylor
    • , Alexander Teumer
    • , Timothy A. Thornton
    • , Lesley E. Tinker
    • , André G. Uitterlinden
    • , Jessica van Setten
    • , Andreas Voss
    • , Melanie Waldenberger
    • , Kirk C. Wilhelmsen
    • , Gonneke Willemsen
    • , Quenna Wong
    • , Zhu-Ming Zhang
    • , Alan B. Zonderman
    • , Daniele Cusi
    • , Michele K. Evans
    • , Halina K. Greiser
    • , Pim van der Harst
    • , Mohammad Hassan
    • , Erik Ingelsson
    • , Marjo-Riitta Järvelin
    • , Stefan Kääb
    • , Mika Kähönen
    • , Mika Kivimaki
    • , Charles Kooperberg
    • , Diana Kuh
    • , Terho Lehtimäki
    • , Lars Lind
    • , Caroline M. Nievergelt
    • , Chris J. O'Donnell
    • , Albertine J. Oldehinkel
    • , Brenda Penninx
    • , Alexander P. Reiner
    • , Harriëtte Riese
    • , Arie M. van Roon
    • , John D. Rioux
    • , Jerome I. Rotter
    • , Tamar Sofer
    • , Bruno H. Stricker
    • , Henning Tiemeier
    • , Tanja G. M. Vrijkotte
    • , Folkert W. Asselbergs
    • , Bianca J. J. M. Brundel
    • , Susan R. Heckbert
    • , Eric A. Whitsel
    • , Marcel den Hoed
    • , Harold Snieder
    •  & Eco J. C. de Geus
  • Article
    | Open Access

    Endometriosis is a major cause of infertility. Molecular mechanisms underlying the disease involve genetic and environmental risk factors. In a meta-analysis of eleven GWA studies, Sapkota and colleagues identify five novel risk loci, implicating steroid sex hormone pathways in the pathogenesis.

    • Yadav Sapkota
    • , Valgerdur Steinthorsdottir
    • , Andrew P. Morris
    • , Amelie Fassbender
    • , Nilufer Rahmioglu
    • , Immaculata De Vivo
    • , Julie E. Buring
    • , Futao Zhang
    • , Todd L. Edwards
    • , Sarah Jones
    • , Dorien O
    • , Daniëlle Peterse
    • , Kathryn M. Rexrode
    • , Paul M. Ridker
    • , Andrew J. Schork
    • , Stuart MacGregor
    • , Nicholas G. Martin
    • , Christian M. Becker
    • , Sosuke Adachi
    • , Kosuke Yoshihara
    • , Takayuki Enomoto
    • , Atsushi Takahashi
    • , Yoichiro Kamatani
    • , Koichi Matsuda
    • , Michiaki Kubo
    • , Gudmar Thorleifsson
    • , Reynir T. Geirsson
    • , Unnur Thorsteinsdottir
    • , Leanne M. Wallace
    • , Thomas M. Werge
    • , Wesley K. Thompson
    • , Jian Yang
    • , Digna R. Velez Edwards
    • , Mette Nyegaard
    • , Siew-Kee Low
    • , Krina T. Zondervan
    • , Stacey A. Missmer
    • , Thomas D'Hooghe
    • , Grant W. Montgomery
    • , Daniel I. Chasman
    • , Kari Stefansson
    • , Joyce Y. Tung
    •  & Dale R. Nyholt
  • Article
    | Open Access

    Lumbar disc herniation (LDH) can cause persistent sciatica, and in some cases surgery is required to relieve symptoms. Here, the authors carry out a genome-wide association study using microdiscectomy as an indicator of severe LDH, and find a locus on chromosome 8 associated with this condition.

    • Gyda Bjornsdottir
    • , Stefania Benonisdottir
    • , Gardar Sveinbjornsson
    • , Unnur Styrkarsdottir
    • , Gudmar Thorleifsson
    • , G. Bragi Walters
    • , Aron Bjornsson
    • , Ingvar H. Olafsson
    • , Elfar Ulfarsson
    • , Arnor Vikingsson
    • , Ragnheidur Hansdottir
    • , Karl O. Karlsson
    • , Thorunn Rafnar
    • , Ingileif Jonsdottir
    • , Michael L. Frigge
    • , Augustine Kong
    • , Asmundur Oddsson
    • , Gisli Masson
    • , Olafur T. Magnusson
    • , Tomas Gudbjartsson
    • , Hreinn Stefansson
    • , Patrick Sulem
    • , Daniel Gudbjartsson
    • , Unnur Thorsteinsdottir
    • , Thorgeir E. Thorgeirsson
    •  & Kari Stefansson
  • Article
    | Open Access

    Some adolescents seek novelty, but it is unknown whether the brain circuits underlying this behaviour can be used to predict later, problematic behaviour. Here, authors show that diminished ventral striatal and prefrontal activity in response to anticipated rewards at age 14 in these individuals predicts problematic drug use at age 16.

    • Christian Büchel
    • , Jan Peters
    • , Tobias Banaschewski
    • , Arun L. W. Bokde
    • , Uli Bromberg
    • , Patricia J. Conrod
    • , Herta Flor
    • , Dimitri Papadopoulos
    • , Hugh Garavan
    • , Penny Gowland
    • , Andreas Heinz
    • , Henrik Walter
    • , Bernd Ittermann
    • , Karl Mann
    • , Jean-Luc Martinot
    • , Marie-Laure Paillère-Martinot
    • , Frauke Nees
    • , Tomas Paus
    • , Zdenka Pausova
    • , Luise Poustka
    • , Marcella Rietschel
    • , Trevor W. Robbins
    • , Michael N. Smolka
    • , Juergen Gallinat
    • , Gunter Schumann
    • , Brian Knutson
    • , Mercedes Arroyo
    • , Eric Artiges
    • , Semiha Aydin
    • , Christine Bach
    • , Alexis Barbot
    • , Gareth Barker
    • , Ruediger Bruehl
    • , Anna Cattrell
    • , Patrick Constant
    • , Hans Crombag
    • , Katharina Czech
    • , Jeffrey Dalley
    • , Benjamin Decideur
    • , Sylvane Desrivieres
    • , Tahmine Fadai
    • , Mira Fauth-Buhler
    • , Jianfeng Feng
    • , Irinia Filippi
    • , Vincent Frouin
    • , Birgit Fuchs
    • , Isabel Gemmeke
    • , Alexander Genauck
    • , Eanna Hanratty
    • , Bert Heinrichs
    • , Nadja Heym
    • , Thomas Hubner
    • , Albrecht Ihlenfeld
    • , Alex Ing
    • , James Ireland
    • , Tianye Jia
    • , Jennifer Jones
    • , Sarah Jurk
    • , Mehri Kaviani
    • , Arno Klaassen
    • , Johann Kruschwitz
    • , Christophe Lalanne
    • , Dirk Lanzerath
    • , Mark Lathrop
    • , Claire Lawrence
    • , Hervé Lemaitre
    • , Christine Macare
    • , Catherine Mallik
    • , Adam Mar
    • , Lourdes Martinez-Medina
    • , Eva Mennigen
    • , Fabiana Mesquita de Carvahlo
    • , Xavier Mignon
    • , Sabina Millenet
    • , Ruben Miranda
    • , Kathrin Müller
    • , Charlotte Nymberg
    • , Caroline Parchetka
    • , Yolanda Pena-Oliver
    • , Jani Pentilla
    • , Jean-Baptiste Poline
    • , Erin Burke Quinlan
    • , Michael Rapp
    • , Stephan Ripke
    • , Tamzin Ripley
    • , Gabriel Robert
    • , John Rogers
    • , Alexander Romanowski
    • , Barbara Ruggeri
    • , Christine Schmäl
    • , Dirk Schmidt
    • , Sophia Schneider
    • , Florian Schubert
    • , Yannick Schwartz
    • , Wolfgang Sommer
    • , Rainer Spanagel
    • , Claudia Speiser
    • , Tade Spranger
    • , Alicia Stedman
    • , Dai Stephens
    • , Nicole Strache
    • , Andreas Ströhle
    • , Maren Struve
    • , Naresh Subramaniam
    • , David Theobald
    • , Nora Vetter
    • , Helene Vulser
    • , Katharina Weiss
    • , Robert Whelan
    • , Steve Williams
    • , Bing Xu
    • , Juliana Yacubian
    • , Tao Yu
    •  & Veronika Ziesch
  • Article
    | Open Access

    Coronary heart disease is the leading cause of death worldwide with multiple environmental and genetic risk factors. Here the authors integrate genomic, epigenomic and transcriptomic mapping to elucidate causal variation and mechanisms of known genetic associations.

    • Clint L. Miller
    • , Milos Pjanic
    • , Ting Wang
    • , Trieu Nguyen
    • , Ariella Cohain
    • , Jonathan D. Lee
    • , Ljubica Perisic
    • , Ulf Hedin
    • , Ramendra K. Kundu
    • , Deshna Majmudar
    • , Juyong B. Kim
    • , Oliver Wang
    • , Christer Betsholtz
    • , Arno Ruusalepp
    • , Oscar Franzén
    • , Themistocles L. Assimes
    • , Stephen B. Montgomery
    • , Eric E. Schadt
    • , Johan L.M. Björkegren
    •  & Thomas Quertermous
  • Article
    | Open Access

    Sudden arrhythmic death is a leading cause of mortality, however approaches to identify at-risk patients are of low sensitivity and specificity. Here, the authors develop a personalized approach to assess arrhythmia risk in post-infarction patients based on cardiac imaging and computational modelling that significantly outperforms existing clinical metrics.

    • Hermenegild J. Arevalo
    • , Fijoy Vadakkumpadan
    • , Eliseo Guallar
    • , Alexander Jebb
    • , Peter Malamas
    • , Katherine C. Wu
    •  & Natalia A. Trayanova
  • Article |

    African Americans have much higher colon cancer rates than rural South Africans, which is associated with dietary and metabolic differences. Here, O’Keefe et al.show that switching quantities of fat and fibre leads to reciprocal changes in gut microbiota, metabolites and cancer biomarkers.

    • Stephen J. D. O’Keefe
    • , Jia V. Li
    • , Leo Lahti
    • , Junhai Ou
    • , Franck Carbonero
    • , Khaled Mohammed
    • , Joram M. Posma
    • , James Kinross
    • , Elaine Wahl
    • , Elizabeth Ruder
    • , Kishore Vipperla
    • , Vasudevan Naidoo
    • , Lungile Mtshali
    • , Sebastian Tims
    • , Philippe G. B. Puylaert
    • , James DeLany
    • , Alyssa Krasinskas
    • , Ann C. Benefiel
    • , Hatem O. Kaseb
    • , Keith Newton
    • , Jeremy K. Nicholson
    • , Willem M. de Vos
    • , H. Rex Gaskins
    •  & Erwin G. Zoetendal
  • Article
    | Open Access

    Age-related macular degeneration (AMD) is a major cause of blindness worldwide. Here, the authors carry out a two-stage genome-wide association study for AMD and identify three new AMD risk loci, highlighting the shared and distinct genetic basis of the disease in East Asians and Europeans.

    • Ching-Yu Cheng
    • , Kenji Yamashiro
    • , Li Jia Chen
    • , Jeeyun Ahn
    • , Lulin Huang
    • , Lvzhen Huang
    • , Chui Ming G. Cheung
    • , Masahiro Miyake
    • , Peter D. Cackett
    • , Ian Y. Yeo
    • , Augustinus Laude
    • , Ranjana Mathur
    • , Junxiong Pang
    • , Kar Seng Sim
    • , Adrian H. Koh
    • , Peng Chen
    • , Shu Yen Lee
    • , Doric Wong
    • , Choi Mun Chan
    • , Boon Kwang Loh
    • , Yaoyao Sun
    • , Sonia Davila
    • , Isao Nakata
    • , Hideo Nakanishi
    • , Yumiko Akagi-Kurashige
    • , Norimoto Gotoh
    • , Akitaka Tsujikawa
    • , Fumihiko Matsuda
    • , Keisuke Mori
    • , Shin Yoneya
    • , Yoichi Sakurada
    • , Hiroyuki Iijima
    • , Tomohiro Iida
    • , Shigeru Honda
    • , Timothy Yuk Yau Lai
    • , Pancy Oi Sin Tam
    • , Haoyu Chen
    • , Shibo Tang
    • , Xiaoyan Ding
    • , Feng Wen
    • , Fang Lu
    • , Xiongze Zhang
    • , Yi Shi
    • , Peiquan Zhao
    • , Bowen Zhao
    • , Jinghong Sang
    • , Bo Gong
    • , Rajkumar Dorajoo
    • , Jian-Min Yuan
    • , Woon-Puay Koh
    • , Rob M. van Dam
    • , Yechiel Friedlander
    • , Ying Lin
    • , Martin L. Hibberd
    • , Jia Nee Foo
    • , Ningli Wang
    • , Chang Hua Wong
    • , Gavin S. Tan
    • , Sang Jun Park
    • , Mayuri Bhargava
    • , Lingam Gopal
    • , Thet Naing
    • , Jiemin Liao
    • , Peng Guan Ong
    • , Paul Mitchell
    • , Peng Zhou
    • , Xuefeng Xie
    • , Jinlong Liang
    • , Junpu Mei
    • , Xin Jin
    • , Seang-Mei Saw
    • , Mineo Ozaki
    • , Takanori Mizoguchi
    • , Yasuo Kurimoto
    • , Se Joon Woo
    • , Hum Chung
    • , Hyeong-Gon Yu
    • , Joo Young Shin
    • , Dong Ho Park
    • , In Taek Kim
    • , Woohyok Chang
    • , Min Sagong
    • , Sang-Joon Lee
    • , Hyun Woong Kim
    • , Ji Eun Lee
    • , Yi Li
    • , Jianjun Liu
    • , Yik Ying Teo
    • , Chew Kiat Heng
    • , Tock Han Lim
    • , Suk-Kyun Yang
    • , Kyuyoung Song
    • , Eranga N. Vithana
    • , Tin Aung
    • , Jin Xin Bei
    • , Yi Xin Zeng
    • , E. Shyong Tai
    • , Xiao Xin Li
    • , Zhenglin Yang
    • , Kyu-Hyung Park
    • , Chi Pui Pang
    • , Nagahisa Yoshimura
    • , Tien Yin Wong
    •  & Chiea Chuen Khor
  • Article |

    A link between smoking and the incidence of Alzheimer’s disease has been implicated in humans. In this study, transgenic mouse models of Alzheimer’s disease exposed to cigarette smoke display increased disease abnormalities in the brain, such as amyloidogenesis, neuroinflammation and tau phosphorylation.

    • Ines Moreno-Gonzalez
    • , Lisbell D. Estrada
    • , Elisabeth Sanchez-Mejias
    •  & Claudio Soto