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Effect of Loss-of-Function Genetic Variants in PCSK9 on Glycemic Traits, Neurocognitive Impairment, and Hepatobiliary Function

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@article{164e0ccfb8ab4a0db7fc965d76e91eb6,
title = "Effect of Loss-of-Function Genetic Variants in PCSK9 on Glycemic Traits, Neurocognitive Impairment, and Hepatobiliary Function",
abstract = "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 = 7.4 × 10-55) and apolipoprotein B levels (P = 7.6 × 10-50) 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.",
author = "Jonas Ghouse and Gustav Ahlberg and Henning Bundgaard and Olesen, {Morten S}",
note = "{\textcopyright} 2021 by the American Diabetes Association.",
year = "2022",
month = jan,
day = "1",
doi = "10.2337/dc21-0955",
language = "English",
volume = "45",
pages = "251--254",
journal = "Diabetes Care",
issn = "1935-5548",
publisher = "American Diabetes Association",
number = "1",

}

RIS

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 - © 2021 by the American Diabetes Association.

PY - 2022/1/1

Y1 - 2022/1/1

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 = 7.4 × 10-55) and apolipoprotein B levels (P = 7.6 × 10-50) 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 = 7.4 × 10-55) and apolipoprotein B levels (P = 7.6 × 10-50) 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

VL - 45

SP - 251

EP - 254

JO - Diabetes Care

JF - Diabetes Care

SN - 1935-5548

IS - 1

ER -

ID: 75303633