{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T17:56:34Z","timestamp":1783619794365,"version":"3.55.0"},"reference-count":76,"publisher":"S. Karger AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,6]],"date-time":"2021-12-06T00:00:00Z","timestamp":1638748800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2021,12,6]],"date-time":"2021-12-06T00:00:00Z","timestamp":1638748800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Lifestyle Genomics"],"published-print":{"date-parts":[[2022]]},"abstract":"<jats:p>&lt;b&gt;&lt;i&gt;Background:&lt;\/i&gt;&lt;\/b&gt; \u201cQuantile-dependent expressivity\u201d is a dependence of genetic effects on whether the phenotype (e.g., insulin resistance) is high or low relative to its distribution. &lt;b&gt;&lt;i&gt;Methods:&lt;\/i&gt;&lt;\/b&gt; Quantile-specific offspring-parent regression slopes (\u03b2&lt;sub&gt;OP&lt;\/sub&gt;) were estimated by quantile regression for fasting glucose concentrations in 6,453 offspring-parent pairs from the Framingham Heart Study. &lt;b&gt;&lt;i&gt;Results:&lt;\/i&gt;&lt;\/b&gt; Quantile-specific heritability (&lt;i&gt;h&lt;\/i&gt;&lt;sup&gt;2&lt;\/sup&gt;), estimated by 2\u03b2&lt;sub&gt;OP&lt;\/sub&gt;\/(1 + &lt;i&gt;r&lt;\/i&gt;&lt;sub&gt;spouse&lt;\/sub&gt;), increased 0.0045 \u00b1 0.0007 (&lt;i&gt;p&lt;\/i&gt; = 8.8 \u00d7 10&lt;sup&gt;\u221214&lt;\/sup&gt;) for each 1% increment in the fasting glucose distribution, that is, &lt;i&gt;h&lt;\/i&gt;&lt;sup&gt;2&lt;\/sup&gt; \u00b1 SE were 0.057 \u00b1 0.021, 0.095 \u00b1 0.024, 0.146 \u00b1 0.019, 0.293 \u00b1 0.038, and 0.456 \u00b1 0.061 at the 10th, 25th, 50th, 75th, and 90th percentiles of the fasting glucose distribution, respectively. Significant increases in quantile-specific heritability were also suggested for fasting insulin (&lt;i&gt;p&lt;\/i&gt; = 1.2 \u00d7 10&lt;sup&gt;\u22126&lt;\/sup&gt;), homeostatic model assessment of insulin resistance (HOMA-IR, &lt;i&gt;p&lt;\/i&gt; = 5.3 \u00d7 10&lt;sup&gt;\u22125&lt;\/sup&gt;), insulin\/glucose ratio (&lt;i&gt;p&lt;\/i&gt; = 3.9 \u00d7 10&lt;sup&gt;\u22125&lt;\/sup&gt;), proinsulin (&lt;i&gt;p&lt;\/i&gt; = 1.4 \u00d7 10&lt;sup&gt;\u22126&lt;\/sup&gt;), proinsulin\/insulin ratio (&lt;i&gt;p&lt;\/i&gt; = 2.7 \u00d7 10&lt;sup&gt;\u22125&lt;\/sup&gt;), and glucose concentrations during a glucose tolerance test (&lt;i&gt;p&lt;\/i&gt; = 0.001), and their logarithmically transformed values. &lt;b&gt;&lt;i&gt;Discussion\/Conclusion:&lt;\/i&gt;&lt;\/b&gt; These findings suggest alternative interpretations to precision medicine and gene-environment interactions, including alternative interpretation of reported synergisms between &lt;i&gt;ACE, ADRB3&lt;\/i&gt;, &lt;i&gt;PPAR-\u03b32&lt;\/i&gt;, and &lt;i&gt;TNF-\u03b1&lt;\/i&gt; polymorphisms and being born small for gestational age on adult insulin resistance (fetal origin theory), and gene-adiposity (&lt;i&gt;APOE, ENPP1, GCKR, IGF2BP2, IL-6, IRS-1, KIAA0280, LEPR, MFHAS1, RETN, TCF7L2&lt;\/i&gt;), gene-exercise (&lt;i&gt;INS&lt;\/i&gt;), gene-diet (&lt;i&gt;ACSL1&lt;\/i&gt;, &lt;i&gt;ELOVL6&lt;\/i&gt;, &lt;i&gt;IRS-1&lt;\/i&gt;, &lt;i&gt;PLIN&lt;\/i&gt;, &lt;i&gt;S100A9&lt;\/i&gt;), and gene-socioeconomic interactions. <\/jats:p>","DOI":"10.1159\/000519382","type":"journal-article","created":{"date-parts":[[2021,12,6]],"date-time":"2021-12-06T22:00:45Z","timestamp":1638828045000},"page":"10-34","source":"Crossref","is-referenced-by-count":2,"title":["Quantile-Dependent Heritability of Glucose, Insulin, Proinsulin, Insulin Resistance, and Glycated Hemoglobin"],"prefix":"10.1159","volume":"15","author":[{"given":"Paul 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