Genome-wide association study identifying novel variant for fasting insulin and allelic heterogeneity in known glycemic loci in chilean adolescents: The Santiago longitudinal study

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 (beta = -0.299, SE = 0.054, p = 2.72x10(-8)) and was only slightly attenuated after adjusting for body mass index z-scores (beta = -0.252, SE = 0.047, p = 1.03x10(-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.

American Diabetes Association 1-19-PDF-045 American Heart Association 15GRNT25880008 United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Cancer Institute (NCI) U01CA164973 United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Heart Lung & Blood Institute (NHLBI) HHSN268201100001C HHSN268201100002C HHSN268201100003C HHSN268201100004C HHSN268201100046C HHSN268201200008I HHSN271201100004C K99/R00HL130580 N01-HC65233 N01-HC65234 N01-HC65235 N01-HC65236 N01-HC65237 R01HL088530 R01HL142825 T32 HL007055 T32 HL129982-03 United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Human Genome Research Institute (NHGRI) U01HG007376 U01HG007397 U01HG007419 United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) R01 HD33487 United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute on Minority Health & Health Disparities (NIMHD) U01HG007416 North Carolina Nutrition Research Institute