Genome‐wide association study identifying novel variant for fasting insulin and allelic heterogeneity in known glycemic loci in Chilean adolescents: The Santiago Longitudinal Study
Year: 2020
Type: article
Study design: Observational Study
Abstract: Summary Background The genetic underpinnings of glycemic traits have been understudied in adolescent and Hispanic/Latino (H/L) populations in comparison to adults and populations of European ancestry. Objective To identify genetic factors underlying glycemic traits in an adolescent H/L population. Methods We conducted a genome‐wide association study (GWAS) of fasting glucose (FG) and fasting insulin (FI) in H/L adolescents from the Santiago Longitudinal Study. Results We identified one novel variant positioned in the CSMD1 gene on chromosome 8 (rs77465890, effect allele frequency = 0.10) that was associated with FI (β = −0.299, SE = 0.054, p = 2.72×10−8) and was only slightly attenuated after adjusting for body mass index z‐scores (β = −0.252, SE = 0.047, p = 1.03×10−7). We demonstrated directionally consistent, but not statistically significant results in African and Hispanic adults of the Population Architecture Using Genomics and Epidemiology Consortium. We also identified secondary signals for two FG loci after conditioning on known variants, which demonstrate allelic heterogeneity in well‐known glucose loci. Conclusion Our results exemplify the importance of including populations with diverse ancestral origin and adolescent participants in GWAS of glycemic traits to uncover novel risk loci and expand our understanding of disease aetiology.
Source: Pediatric Obesity
DOI: 10.1111/ijpo.12765
Authors: Victoria L Buchanan, Yujie Wang, Estela Blanco, Mariaelisa Graff, Cecilia Albala, Raquel Burrows, José L Santos, Bárbara Angel, Betsy Lozoff, Venkata Saroja Voruganti, Xiuqing Guo, Kent D Taylor, Yii‐Der Ida Chen, Jie Yao, Jingyi Tan, Carolina Downie, Heather M Highland, Anne E Justice, Sheila Gahagan, Kari E North
Institutions: University of North Carolina at Chapel Hill, University of California San Diego, University of Chile, Pontificia Universidad Católica de Chile, University of Michigan, Michigan Medicine, University of California, Los Angeles, The Lundquist Institute, Harbor–UCLA Medical Center, Geisinger Medical Center, Geisinger Health System
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
Funders: American Diabetes Association, American Heart Association, National Institutes of Health, National Institute on Aging, National Heart, Lung, and Blood Institute, National Human Genome Research Institute, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Child Health and Human Development, National Center for Research Resources, National Center for Advancing Translational Sciences, National Institute on Minority Health and Health Disparities, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1081972346, G1312369436, Continuation of the Nonalcoholic Steatohepatitis Clinical Research Network, Hispanic Community Health Study, San Diego Clinical and Translational Research Institute, G1455175283, Clinical and Translational Science Institute, G1666450717, Biopsychosocial Determinants of Adolescent Obesity-Cardiovascular Risk, G1947136479, G2273349799, Case Western Reserve University/Cleveland Clinic CTSA (UL1), G2412562481, G2466919156, Clinical and Translational Science Award, HISPANIC COMMUNITY HEALTH STUDY - FIELD CENTER, G2528054427, G2636451769, G2644289446, Mount Sinai Institutes for Clinical and Translational Sciences, G2859924462, G2970637568, G3226771441, Hispanic Community Health Study, G3545534745, Genetic Epidemiology of Causal Variants across the Life Course Phase II (CALiCo I, Exome Variants Underlying Weight Gain from Adolescence to Adulthood, G3796112702, G3824871896, Institute for Translational Health Science (UL1), G412187901, G4240450635, Sex- and Smoking- Specific DNA Methylation Signatures of Central Adiposity Change, Hispanic Community Health Study, G4407350458, A 7 Tesla MRI Scanner for Small Animal Imaging Research, Genetic and Environmental Determinants of Obesity and CVD Risk across the Lifecourse: The Santiago Longitudinal Study, Indiana Clinical and Translational Science Institute (UL1), G5365244667, HISPANIC COMMUNITY HEALTH STUDY - COORDINATING CENTER, Epidemiologic Studies of Putative Functional Variation in Multiethnic Cohort, G5547620395, G5624510383, Leveraging multi-omics approaches to examine metabolic challenges of obesity in relation to cardiovascular diseases, G6075306088, G614814196, G619791618, Leveraging ancestral diversity to map adiposity loci in Hispanics, Center for Clinical and Translational Research, G673128162, G6967911674, General Clinical Research Center, NHGRI PAGE Coordinating Center, Sex- and Smoking- Specific DNA Methylation Signatures of Central Adiposity Change, Resilience to obesity in carriers of monogenic obesity mutations - a study on the underlying mechanisms, Multidisciplinary Clinical and Translational Science (MCTS) Program (UL1), Neuromaturational Delays in Iron Deficient Anemic Infants, Clinical and Translational Science Award, G8536616440, Exonic variants and their relation to complex traits in minorities of the WHI, Characterizing pleiotropy in cardiometabolic phenotypes among diverse populations, Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN), Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN), Diabetes Research Center (DRC), Clinical Research Network in Nonalcoholic Steatohepatitis, Cardiovascular Epidemiology Training Grant, Collaborative Clinical Research in Nonalcoholic Steatohepatitis, The Genetic Epidemiology of Heart, Lung, and Blood Traits Training Grant (GenHLB), Hispanic Latino Lipid Consortium, Continuation of the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Clinical Center-Cleveland site, Understanding Population Differences in Cancer: The MEC Study, Clinical Research on Nonalcoholic Fatty Liver Disease, The Saint Louis University Component of the NASH Clinical Research Network, Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN)
OpenAlex ID: W3117189050