Heritability analysis with repeat measurements and its application to resting-state functional connectivity.
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Abstract | Heritability, defined as the proportion of phenotypic variation attributable to genetic variation, provides important information about the genetic basis of a trait. Existing heritability analysis methods do not discriminate between stable effects (e.g., due to the subject's unique environment) and transient effects, such as measurement error. This can lead to misleading assessments, particularly when comparing the heritability of traits that exhibit different levels of reliability. Here, we present a linear mixed effects model to conduct heritability analyses that explicitly accounts for intrasubject fluctuations (e.g., due to measurement noise or biological transients) using repeat measurements. We apply the proposed strategy to the analysis of resting-state fMRI measurements-a prototypic data modality that exhibits variable levels of test-retest reliability across space. Our results reveal that the stable components of functional connectivity within and across well-established large-scale brain networks can be considerably heritable. Furthermore, we demonstrate that dissociating intra- and intersubject variation can reveal genetic influence on a phenotype that is not fully captured by conventional heritability analyses. |
Year of Publication | 2017
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Journal | Proc Natl Acad Sci U S A
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Volume | 114
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Issue | 21
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Pages | 5521-5526
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Date Published | 2017 05 23
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ISSN | 1091-6490
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DOI | 10.1073/pnas.1700765114
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PubMed ID | 28484032
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PubMed Central ID | PMC5448225
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Grant list | R01 NS070963 / NS / NINDS NIH HHS / United States
K25 EB013649 / EB / NIBIB NIH HHS / United States
K24 MH094614 / MH / NIMH NIH HHS / United States
R41 AG052246 / AG / NIA NIH HHS / United States
U54 MH091657 / MH / NIMH NIH HHS / United States
K01 MH099232 / MH / NIMH NIH HHS / United States
R21 AG050122 / AG / NIA NIH HHS / United States
S10 RR023043 / RR / NCRR NIH HHS / United States
P41 EB015896 / EB / NIBIB NIH HHS / United States
R01 NS083534 / NS / NINDS NIH HHS / United States
S10 RR023401 / RR / NCRR NIH HHS / United States
R01 MH101486 / MH / NIMH NIH HHS / United States
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