Effect of Loss-of-Function Genetic Variants in PCSK9 on Glycemic Traits, Neurocognitive Impairment, and Hepatobiliary Function
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Effect of Loss-of-Function Genetic Variants in PCSK9 on Glycemic Traits, Neurocognitive Impairment, and Hepatobiliary Function. / Ghouse, Jonas; Ahlberg, Gustav; Bundgaard, Henning; Olesen, Morten S.
I: Diabetes Care, Bind 45, Nr. 1, 2022, s. 251-254.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Effect of Loss-of-Function Genetic Variants in PCSK9 on Glycemic Traits, Neurocognitive Impairment, and Hepatobiliary Function
AU - Ghouse, Jonas
AU - Ahlberg, Gustav
AU - Bundgaard, Henning
AU - Olesen, Morten S.
N1 - Publisher Copyright: © 2021 by the American Diabetes Association.
PY - 2022
Y1 - 2022
N2 - OBJECTIVE To evaluate the association between PCSK9 predicted loss-of-function (pLoF) variants and glycemic traits, hepatobiliary function, and neurocognitive traits. RESEARCH DESIGN AND METHODS We identified carriers of PCSK9 pLoF variants in UK Biobank exome sequencing data. We assessed the aggregate effects of these variants on lipid and lipoprotein traits, which served as a positive control. Association of PCSK9 pLoF carrier status and glycemic traits, hepatobiliary function, and neurocognitive traits was then evaluated as a measure for adverse effects. RESULTS We identified 374 individuals carrying one of 41 unique PCSK9 pLoF variants. As expected, we found that PCSK9 pLoF carriers had significantly lower LDL cholesterol C levels (P 5 7.4 × 10255 ) and apolipoprotein B levels (P 5 7.6 × 10250 ) than did noncarriers. However, we found no significant associations between pLoF carrier status and glycemic traits, hepatobiliary function, and neurocognitive traits (P > 0.05). CONCLUSIONS Our results do not support adverse effects of PCSK9 pLoF variants on glycemic traits, hepatobiliary function, or neurocognitive traits.
AB - OBJECTIVE To evaluate the association between PCSK9 predicted loss-of-function (pLoF) variants and glycemic traits, hepatobiliary function, and neurocognitive traits. RESEARCH DESIGN AND METHODS We identified carriers of PCSK9 pLoF variants in UK Biobank exome sequencing data. We assessed the aggregate effects of these variants on lipid and lipoprotein traits, which served as a positive control. Association of PCSK9 pLoF carrier status and glycemic traits, hepatobiliary function, and neurocognitive traits was then evaluated as a measure for adverse effects. RESULTS We identified 374 individuals carrying one of 41 unique PCSK9 pLoF variants. As expected, we found that PCSK9 pLoF carriers had significantly lower LDL cholesterol C levels (P 5 7.4 × 10255 ) and apolipoprotein B levels (P 5 7.6 × 10250 ) than did noncarriers. However, we found no significant associations between pLoF carrier status and glycemic traits, hepatobiliary function, and neurocognitive traits (P > 0.05). CONCLUSIONS Our results do not support adverse effects of PCSK9 pLoF variants on glycemic traits, hepatobiliary function, or neurocognitive traits.
UR - http://www.scopus.com/inward/record.url?scp=85122836721&partnerID=8YFLogxK
U2 - 10.2337/dc21-0955
DO - 10.2337/dc21-0955
M3 - Journal article
C2 - 34758978
AN - SCOPUS:85122836721
VL - 45
SP - 251
EP - 254
JO - Diabetes Care
JF - Diabetes Care
SN - 0149-5992
IS - 1
ER -
ID: 291226983