Publications

2018
Han Chen, Brian E Cade, Kevin J Gleason, Andrew C Bjonnes, Adrienne M Stilp, Tamar Sofer, Matthew P Conomos, Sonia Ancoli-Israel, Raanan Arens, Ali Azarbarzin, and others. 2018. “Multiethnic meta-analysis identifies RAI1 as a possible obstructive sleep apnea–related quantitative trait locus in men.” American journal of respiratory cell and molecular biology, 58, 3, Pp. 391–401.
Han Chen, Brian E Cade, Kevin J Gleason, Andrew C Bjonnes, Adrienne M Stilp, Tamar Sofer, Matthew P Conomos, Sonia Ancoli-Israel, Raanan Arens, Ali Azarbarzin, Graeme I Bell, Jennifer E Below, Sung Chun, Daniel S Evans, Ralf Ewert, Alexis C Frazier-Wood, Sina A Gharib, José Haba-Rubio, Erika W Hagen, Raphael Heinzer, David R Hillman, Craig W Johnson, Zoltan Kutalik, Jacqueline M Lane, Emma K Larkin, Seung Ku Lee, Jingjing Liang, Jose S Loredo, Sutapa Mukherjee, Lyle J Palmer, George J Papanicolaou, Thomas Penzel, Paul E Peppard, Wendy S Post, Alberto R Ramos, Ken Rice, Jerome I Rotter, Scott A Sands, Neomi A Shah, Chol Shin, Katie L Stone, Beate Stubbe, Jae Hoon Sul, Mehdi Tafti, Kent D Taylor, Alexander Teumer, Timothy A Thornton, Gregory J Tranah, Chaolong Wang, Heming Wang, Simon C Warby, Andrew D Wellman, Phyllis C Zee, Craig L Hanis, Cathy C Laurie, Daniel J Gottlieb, Sanjay R Patel, Xiaofeng Zhu, Shamil R Sunyaev, Richa Saxena, Xihong Lin, and Susan Redline. 2018. “Multiethnic Meta-Analysis Identifies RAI1 as a Possible Obstructive Sleep Apnea-related Quantitative Trait Locus in Men.” Am J Respir Cell Mol Biol, 58, 3, Pp. 391-401.Abstract
Obstructive sleep apnea (OSA) is a common heritable disorder displaying marked sexual dimorphism in disease prevalence and progression. Previous genetic association studies have identified a few genetic loci associated with OSA and related quantitative traits, but they have only focused on single ethnic groups, and a large proportion of the heritability remains unexplained. The apnea-hypopnea index (AHI) is a commonly used quantitative measure characterizing OSA severity. Because OSA differs by sex, and the pathophysiology of obstructive events differ in rapid eye movement (REM) and non-REM (NREM) sleep, we hypothesized that additional genetic association signals would be identified by analyzing the NREM/REM-specific AHI and by conducting sex-specific analyses in multiethnic samples. We performed genome-wide association tests for up to 19,733 participants of African, Asian, European, and Hispanic/Latino American ancestry in 7 studies. We identified rs12936587 on chromosome 17 as a possible quantitative trait locus for NREM AHI in men (N = 6,737; P = 1.7 × 10) but not in women (P = 0.77). The association with NREM AHI was replicated in a physiological research study (N = 67; P = 0.047). This locus overlapping the RAI1 gene and encompassing genes PEMT1, SREBF1, and RASD1 was previously reported to be associated with coronary artery disease, lipid metabolism, and implicated in Potocki-Lupski syndrome and Smith-Magenis syndrome, which are characterized by abnormal sleep phenotypes. We also identified gene-by-sex interactions in suggestive association regions, suggesting that genetic variants for AHI appear to vary by sex, consistent with the clinical observations of strong sexual dimorphism.
Hassan S Dashti, Jordi Merino, Jacqueline M Lane, Jose C Florez, Martin K Rutter, and Richa Saxena. 2018. “Multitrait genome-wide association analysis of macronutrient intake identifies 12 novel loci for dietary intake and unravels genetic overlap with lifestyle traits and cardiometabolic diseases”.
Céline Vetter, Hassan S Dashti, Jacqueline M Lane, Simon G Anderson, Eva S Schernhammer, Martin K Rutter, Richa Saxena, and Frank AJL Scheer. 2018. “Night Shift Work, Genetic Risk, and Type 2 Diabetes in the UK Biobank.” Diabetes Care, 41, 4, Pp. 762-769.Abstract
OBJECTIVE: To examine the effects of past and current night shift work and genetic type 2 diabetes vulnerability on type 2 diabetes odds. RESEARCH DESIGN AND METHODS: In the UK Biobank, we examined associations of current ( = 272,214) and lifetime ( = 70,480) night shift work exposure with type 2 diabetes risk (6,770 and 1,191 prevalent cases, respectively). For 180,704 and 44,141 unrelated participants of European ancestry (4,002 and 726 cases, respectively) with genetic data, we assessed whether shift work exposure modified the relationship between a genetic risk score (comprising 110 single-nucleotide polymorphisms) for type 2 diabetes and prevalent diabetes. RESULTS: Compared with day workers, all current night shift workers were at higher multivariable-adjusted odds for type 2 diabetes (none or rare night shifts: odds ratio [OR] 1.15 [95% CI 1.05-1.26]; some nights: OR 1.18 [95% CI 1.05-1.32]; and usual nights: OR 1.44 [95% CI 1.19-1.73]), except current permanent night shift workers (OR 1.09 [95% CI 0.93-1.27]). Considering a person's lifetime work schedule and compared with never shift workers, working more night shifts per month was associated with higher type 2 diabetes odds (<3/month: OR 1.24 [95% CI 0.90-1.68]; 3-8/month: OR 1.11 [95% CI 0.90-1.37]; and >8/month: OR 1.36 [95% CI 1.14-1.62]; = 0.001). The association between genetic type 2 diabetes predisposition and type 2 diabetes odds was not modified by shift work exposure. CONCLUSIONS: Our findings show that night shift work, especially rotating shift work including night shifts, is associated with higher type 2 diabetes odds and that the number of night shifts worked per month appears most relevant for type 2 diabetes odds. Also, shift work exposure does not modify genetic risk for type 2 diabetes, a novel finding that warrants replication.
Céline Vetter, Hassan S Dashti, Jacqueline M Lane, Simon G Anderson, Eva S Schernhammer, Martin K Rutter, Richa Saxena, and Frank AJL Scheer. 2018. “Night shift work, genetic risk, and type 2 diabetes in the UK biobank.” Diabetes care, 41, 4, Pp. 762–769.
2017
JM Lane, I Vlasac, S Redline, D Ray, M Rutter, and R Saxena. 2017. “0004 GENOME-WIDE ASSOCIATION STUDY FOR SNORING IDENTIFIES NOVEL GENETIC FACTORS AND BIOLOGICAL LINKS TO SLEEP APNEA AND OBESITY.” Sleep, 40, Pp. A2.
JM Lane, S Kyle, K Spiegelhalder, I Vlasac, S Redline, D Ray, M Rutter, and R Saxena. 2017. “0027 A GENETIC LINK BETWEEN SLEEP AND PSYCHIATRIC TRAITS.” Sleep, 40, Pp. A10.
C Vetter, HS Dashti, JM Lane, SG Anderson, ES Schernhammer, MK Rutter, R Saxena, and FA Scheer. 2017. “1013 SHIFT WORK, CHRONOTYPE, AND TYPE 2 DIABETES IN THE UK BIOBANK AND TYPE 2 DIABETES IN THE UK BIOBANK.” Journal of Sleep and Sleep Disorders Research, 40, suppl\_1, Pp. A377–A377.
Naomi R Wray, Stephan Ripke, Manuel Mattheisen, Maciej Trzaskowski, Enda M Byrne, Abdel Abdellaoui, Mark J Adams, Esben Agerbo, Tracy M Air, Till FM Andlauer, and others. 2017. “Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depressive disorder.” bioRxiv, Pp. 167577.
Jacqueline M Lane, Jingjing Liang, Irma Vlasac, Simon G Anderson, David A Bechtold, Jack Bowden, Richard Emsley, Shubhroz Gill, Max A Little, Annemarie I Luik, Andrew Loudon, Frank AJL Scheer, Shaun M Purcell, Simon D Kyle, Deborah A Lawlor, Xiaofeng Zhu, Susan Redline, David W Ray, Martin K Rutter, and Richa Saxena. 2017. “Genome-wide association analyses of sleep disturbance traits identify new loci and highlight shared genetics with neuropsychiatric and metabolic traits.” Nat Genet, 49, 2, Pp. 274-281.Abstract
Chronic sleep disturbances, associated with cardiometabolic diseases, psychiatric disorders and all-cause mortality, affect 25-30% of adults worldwide. Although environmental factors contribute substantially to self-reported habitual sleep duration and disruption, these traits are heritable and identification of the genes involved should improve understanding of sleep, mechanisms linking sleep to disease and development of new therapies. We report single- and multiple-trait genome-wide association analyses of self-reported sleep duration, insomnia symptoms and excessive daytime sleepiness in the UK Biobank (n = 112,586). We discover loci associated with insomnia symptoms (near MEIS1, TMEM132E, CYCL1 and TGFBI in females and WDR27 in males), excessive daytime sleepiness (near AR-OPHN1) and a composite sleep trait (near PATJ (INADL) and HCRTR2) and replicate a locus associated with sleep duration (at PAX8). We also observe genetic correlation between longer sleep duration and schizophrenia risk (r = 0.29, P = 1.90 × 10) and between increased levels of excessive daytime sleepiness and increased measures for adiposity traits (body mass index (BMI): r = 0.20, P = 3.12 × 10; waist circumference: r = 0.20, P = 2.12 × 10).
Jacqueline M Lane, Jingjing Liang, Irma Vlasac, Simon G Anderson, David A Bechtold, Jack Bowden, Richard Emsley, Shubhroz Gill, Max A Little, Annemarie I Luik, and others. 2017. “Genome-wide association analyses of sleep disturbance traits identify new loci and highlight shared genetics with neuropsychiatric and metabolic traits.” Nature genetics, 49, 2, Pp. 274–281.
Tamar Sofer, Quenna Wong, Fernando P Hartwig, Kent Taylor, Helen R Warren, Evangelos Evangelou, Claudia P Cabrera, Daniel Levy, Holly Kramer, Leslie A Lange, Bernardo L Horta, Kathleen F Kerr, Alex P Reiner, and Nora Franceschini. 2017. “Genome-Wide Association Study of Blood Pressure Traits by Hispanic/Latino Background: the Hispanic Community Health Study/Study of Latinos.” Sci Rep, 7, 1, Pp. 10348.Abstract
Hypertension prevalence varies between ethnic groups, possibly due to differences in genetic, environmental, and cultural determinants. Hispanic/Latino Americans are a diverse and understudied population. We performed a genome-wide association study (GWAS) of blood pressure (BP) traits in 12,278 participants from the Hispanics Community Health Study/Study of Latinos (HCHS/SOL). In the discovery phase we identified eight previously unreported BP loci. In the replication stage, we tested these loci in the 1982 Pelotas Birth Cohort Study of admixed Southern Brazilians, the COGENT-BP study of African descent, women of European descent from the Women Health Initiative (WHI), and a sample of European descent from the UK Biobank. No loci met the Bonferroni-adjusted level of statistical significance (0.0024). Two loci had marginal evidence of replication: rs78701042 (NGF) with diastolic BP (P = 0.008 in the 1982 Pelotas Birth Cohort Study), and rs7315692 (SLC5A8) with systolic BP (P = 0.007 in European ancestry replication). We investigated whether previously reported loci associated with BP in studies of European, African, and Asian ancestry generalize to Hispanics/Latinos. Overall, 26% of the known associations in studies of individuals of European and Chinese ancestries generalized, while only a single association previously discovered in a people of African descent generalized.
Dayna A Johnson, Jacqueline Lane, Rui Wang, Michelle Reid, Ina Djonlagic, Annette L Fitzpatrick, Stephen R Rapp, Luenda E Charles, Ruth O’Hara, Richa Saxena, and others. 2017. “Greater cognitive deficits with sleep-disordered breathing among individuals with genetic susceptibility to Alzheimer disease. The multi-ethnic study of atherosclerosis.” Annals of the American Thoracic Society, 14, 11, Pp. 1697–1705.
Josep M Mercader, Rachel G Liao, Avery D Bell, Zachary Dymek, Karol Estrada, Taru Tukiainen, Alicia Huerta-Chagoya, Hortensia Moreno-Mac{\'ıas, Kathleen A Jablonski, Robert L Hanson, and others. 2017. “A loss-of-function splice acceptor variant in IGF2 is protective for type 2 diabetes.” Diabetes, 66, 11, Pp. 2903–2914.
Jingjing Liang, Thu H Le, Digna Velez R Edwards, Bamidele O Tayo, Kyle J Gaulton, Jennifer A Smith, Yingchang Lu, Richard A Jensen, Guanjie Chen, Lisa R Yanek, and others. 2017. “Single-trait and multi-trait genome-wide association analyses identify novel loci for blood pressure in African-ancestry populations.” PLoS genetics, 13, 5, Pp. e1006728.
Jingjing Liang, Thu H Le, Digna Velez R Edwards, Bamidele O Tayo, Kyle J Gaulton, Jennifer A Smith, Yingchang Lu, Richard A Jensen, Guanjie Chen, Lisa R Yanek, Karen Schwander, Salman M Tajuddin, Tamar Sofer, Wonji Kim, James Kayima, Colin A McKenzie, Ervin Fox, Michael A Nalls, Hunter J Young, Yan V Sun, Jacqueline M Lane, Sylvia Cechova, Jie Zhou, Hua Tang, Myriam Fornage, Solomon K Musani, Heming Wang, Juyoung Lee, Adebowale Adeyemo, Albert W Dreisbach, Terrence Forrester, Pei-Lun Chu, Anne Cappola, Michele K Evans, Alanna C Morrison, Lisa W Martin, Kerri L Wiggins, Qin Hui, Wei Zhao, Rebecca D Jackson, Erin B Ware, Jessica D Faul, Alex P Reiner, Michael Bray, Joshua C Denny, Thomas H Mosley, Walter Palmas, Xiuqing Guo, George J Papanicolaou, Alan D Penman, Joseph F Polak, Kenneth Rice, Ken D Taylor, Eric Boerwinkle, Erwin P Bottinger, Kiang Liu, Neil Risch, Steven C Hunt, Charles Kooperberg, Alan B Zonderman, Cathy C Laurie, Diane M Becker, Jianwen Cai, Ruth JF Loos, Bruce M Psaty, David R Weir, Sharon LR Kardia, Donna K Arnett, Sungho Won, Todd L Edwards, Susan Redline, Richard S Cooper, DC Rao, Jerome I Rotter, Charles Rotimi, Daniel Levy, Aravinda Chakravarti, Xiaofeng Zhu, and Nora Franceschini. 2017. “Single-trait and multi-trait genome-wide association analyses identify novel loci for blood pressure in African-ancestry populations.” PLoS Genet, 13, 5, Pp. e1006728.Abstract
Hypertension is a leading cause of global disease, mortality, and disability. While individuals of African descent suffer a disproportionate burden of hypertension and its complications, they have been underrepresented in genetic studies. To identify novel susceptibility loci for blood pressure and hypertension in people of African ancestry, we performed both single and multiple-trait genome-wide association analyses. We analyzed 21 genome-wide association studies comprised of 31,968 individuals of African ancestry, and validated our results with additional 54,395 individuals from multi-ethnic studies. These analyses identified nine loci with eleven independent variants which reached genome-wide significance (P < 1.25×10-8) for either systolic and diastolic blood pressure, hypertension, or for combined traits. Single-trait analyses identified two loci (TARID/TCF21 and LLPH/TMBIM4) and multiple-trait analyses identified one novel locus (FRMD3) for blood pressure. At these three loci, as well as at GRP20/CDH17, associated variants had alleles common only in African-ancestry populations. Functional annotation showed enrichment for genes expressed in immune and kidney cells, as well as in heart and vascular cells/tissues. Experiments driven by these findings and using angiotensin-II induced hypertension in mice showed altered kidney mRNA expression of six genes, suggesting their potential role in hypertension. Our study provides new evidence for genes related to hypertension susceptibility, and the need to study African-ancestry populations in order to identify biologic factors contributing to hypertension.
Simon D Kyle, Claire E Sexton, Bernd Feige, Annemarie I Luik, Jacqueline Lane, Richa Saxena, Simon G Anderson, David A Bechtold, William Dixon, Max A Little, David Ray, Dieter Riemann, Colin A Espie, Martin K Rutter, and Kai Spiegelhalder. 2017. “Sleep and cognitive performance: cross-sectional associations in the UK Biobank.” Sleep Med, 38, Pp. 85-91.Abstract
OBJECTIVE: The relationship between insomnia symptoms and cognitive performance is unclear, particularly at the population level. We conducted the largest examination of this association to date through analysis of the UK Biobank, a large population-based sample of adults aged 40-69 years. We also sought to determine associations between cognitive performance and self-reported chronotype, sleep medication use and sleep duration. METHODS: This cross-sectional, population-based study involved 477,529 participants, comprising 133,314 patients with frequent insomnia symptoms (age: 57.4 ± 7.7 years; 62.1% female) and 344,215 controls without insomnia symptoms (age: 56.1 ± 8.2 years; 52.0% female). Cognitive performance was assessed by a touchscreen test battery probing reasoning, basic reaction time, numeric memory, visual memory, and prospective memory. Adjusted models included relevant demographic, clinical, and sleep variables. RESULTS: Frequent insomnia symptoms were associated with cognitive impairment in unadjusted models; however, these effects were reversed after full adjustment, leaving those with frequent insomnia symptoms showing statistically better cognitive performance over those without. Relative to intermediate chronotype, evening chronotype was associated with superior task performance, while morning chronotype was associated with the poorest performance. Sleep medication use and both long (>9 h) and short (<7 h) sleep durations were associated with impaired performance. CONCLUSIONS: Our results suggest that after adjustment for potential confounding variables, frequent insomnia symptoms may be associated with a small statistical advantage, which is unlikely to be clinically meaningful, on simple neurocognitive tasks. Further work is required to examine the mechanistic underpinnings of an apparent evening chronotype advantage in cognitive performance and the impairment associated with morning chronotype, sleep medication use, and sleep duration extremes.
Simon D Kyle, Claire E Sexton, Bernd Feige, Annemarie I Luik, Jacqueline Lane, Richa Saxena, Simon G Anderson, David A Bechtold, William Dixon, Max A Little, and others. 2017. “Sleep and cognitive performance: cross-sectional associations in the UK Biobank.” Sleep medicine, 38, Pp. 85–91.
Yahtyng Sheu, Francesca Amati, Ann V Schwartz, Michelle E Danielson, Xiaojuan Li, Robert Boudreau, Jane A Cauley, Osteoporotic Fractures Men (MrOS) Research in Group, and others. 2017. “Vertebral bone marrow fat, bone mineral density and diabetes: The Osteoporotic Fractures in Men (MrOS) study.” Bone, 97, Pp. 299–305.
2016
Florian S Eichler, Jiankang Li, Yiran Guo, Paul A Caruso, Andrew C Bjonnes, Jessica Pan, Jessica K Booker, Jacqueline M Lane, Archana Tare, Irma Vlasac, and others. 2016. “CSF1R mosaicism in a family with hereditary diffuse leukoencephalopathy with spheroids.” Brain, 139, 6, Pp. 1666–1672.

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