Beschreibung:
<jats:p>
<jats:bold>Introduction:</jats:bold>
Increased triglycerides (TG) frequently accompanies type 2 diabetes (T2D) mellitus and poor glycemic control. The extent to which genetics influences triglycerides differently in individuals with T2D is not well understood.
</jats:p>
<jats:p>
<jats:bold>Methods:</jats:bold>
We conducted a genome-wide association study (GWAS) of log(TG) stratified by T2D using imputed UKB genotypes with minor allele count>20. We used linear regression model with a leave-one-out cross-validation using REGENIE adjusted for PC1-10, age, age
<jats:sup>2</jats:sup>
, gender, array-type, and race. We assessed the heterogeneity (I
<jats:sup>2</jats:sup>
) between the effects of TG in T2D and non-T2D individuals. We sought replication in the Mass General Brigham Biobank (MGBB).
</jats:p>
<jats:p>
<jats:bold>Results:</jats:bold>
Among 21,176 T2D and 402,944 non-T2D samples, stratified GWAS identified 17 and 45 loci significantly associated with TG levels, respectively. Only one loci exhibited significant genome-wide heterogeneity (I
<jats:sup>2</jats:sup>
=98.4%; p
<jats:sub>heterogeneity</jats:sub>
=2x10
<jats:sup>-15</jats:sup>
). The most significantly heterogenous variant was an intronic variant of the
<jats:italic>HLA-DQB1</jats:italic>
gene, where the major allele (frequency 91.3%) was associated with increased TGs among those with T2D but not non-T2D (T2D group: beta=0.066, p-value=3.9x10
<jats:sup>-15</jats:sup>
; non-T2D group: beta=-0.002, p-value=0.21). Among 25,136 participants (6,951 T2D cases) of MGBB, we replicated this finding (p
<jats:sub>heterogeneity</jats:sub>
=0.01).
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<jats:p>
<jats:bold>Conclusions:</jats:bold>
An intronic variant at
<jats:italic>HLA-DQB1</jats:italic>
significantly associates with increased TGs only in those with T2D.
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