Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution
AuthorPerry, James A.
CHD Exome+ Consortium, Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium
Global Lipids Genetic Consortium
GoT2D Genes Consortium
The MAGIC Investigators
PublisherNature Publishing Group
MetadataShow full item record
AbstractBody-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF <5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants. © 2019, The Author(s)
SponsorsThis work was primarily supported through funding from the National Institute of Health (NIH): 1K99HL130580, R01-DK089256, 2R01HD057194, U01HG007416, R01DK101855, T32 HL007055, KL2TR001109; and the American Heart Association (AHA): 13POST16500011 and 13GRNT16490017. Co-author Y. Jia recently passed away while this work was in process. This study was completed as part of the Genetic Investigation of ANtropometric Traits (GIANT) Consortium. This research has been conducted using the UK Biobank resource. A full list of acknowledgements is provided in the Supplementary Data 18.
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85061697378&doi=10.1038%2fs41588-018-0334-2&partnerID=40&md5=d5ceef119f9dfdbae24734b379330b7b; http://hdl.handle.net/10713/11013
Showing items related by title, author, creator and subject.
The National Behavioral Consortium Benchmarking Study: Industry Profile of 82 External EAP ProvidersAttridge, Mark; Cahill, Terry; Granberry, Stanford Wayne, 1953-; Herlihy, Patricia A. (2013-03-10)It is common practice in many professions, fields and industries to disseminate benchmarking information. Absent this vital resource an individual company cannot accurately evaluate their performance against a similar cohort and therefore must rely upon anecdotal information. The findings of this study address this deficiency in the external Employee Assistance Program (EAP) field by reporting publicly available empirically derived benchmarking data for external providers of EAP services. During 2012 the National Behavioral Consortium conducted a survey that collected data from 82 external EAP vendors primarily located in the United States and Canada. The survey included a total of 44 items organized into eight categories: (1) Company Profile; (2) Staffing; (3) Customer Profile; (4) Utilization Metrics; (5) Survey Tools and Outcomes; (6) Business Management; (7) Business Development; and (8) Forecasting the Future of EAP. The survey respondents included companies that ranged in size from local providers to global business enterprises. The combined customer base represented by these vendors included over 35,000 client companies and over 164 million total covered lives. Results reveal a wide range between vendors on almost all of these factors. Primary findings for utilization include an average case level utilization rate of 4.5% of the covered employee population using the EAP for counseling in the past year (median of 3.6%), with an average of 2.5 counseling sessions delivered per each case. Counseling services were also the most common type of service provided by EAPs, accounting for over 90% of all EAP-related services provided when also considering the use levels for organizational services. In addition to EAP services, 75% of vendors also offered work/life and 49% also offered workplace wellness as “primary” services. Comparisons between smaller and larger market vendors revealed some differences whereas comparisons between countries had few differences. Select benchmarks were also explored between vendors with different pricing models. The role of the Human Resources department at client organizations and product pricing were important themes for business management. Implications for operational practices are discussed along with considerations for future research.