The contribution of common and rare genetic variants to variation in metabolic traits in 288,137 East Asians

Metabolic traits are heritable phenotypes widely-used in assessing the risk of various diseases. We conduct a genome-wide association analysis (GWAS) of nine metabolic traits (including glycemic, lipid, liver enzyme levels) in 125,872 Korean subjects genotyped with the Korea Biobank Array. Following...

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Veröffentlicht in:Nature communications Jg. 13; H. 1; S. 6642 - 13
Hauptverfasser: Kim, Young Jin, Moon, Sanghoon, Hwang, Mi Yeong, Han, Sohee, Jang, Hye-Mi, Kong, Jinhwa, Shin, Dong Mun, Yoon, Kyungheon, Kim, Sung Min, Lee, Jong-Eun, Mahajan, Anubha, Park, Hyun-Young, McCarthy, Mark I., Cho, Yoon Shin, Kim, Bong-Jo
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 04.11.2022
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Asian People - genetics
Association analysis
Biobanks
Blood Glucose - genetics
Diabetes mellitus (non-insulin dependent)
Diabetes Mellitus, Type 2 - genetics
Genetic diversity
Genetic Predisposition to Disease
Genetic variance
Genetic Variation
Genome-Wide Association Study
Genomes
Health risk assessment
Health risks
Humanities and Social Sciences
Humans
Lipids
Meta-analysis
Metabolism
multidisciplinary
Phenotype
Phenotypes
Polygenic inheritance
Polymorphism, Single Nucleotide
Predictions
Risk assessment
Science
Science (multidisciplinary)
ISSN:2041-1723, 2041-1723
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Abstract Metabolic traits are heritable phenotypes widely-used in assessing the risk of various diseases. We conduct a genome-wide association analysis (GWAS) of nine metabolic traits (including glycemic, lipid, liver enzyme levels) in 125,872 Korean subjects genotyped with the Korea Biobank Array. Following meta-analysis with GWAS from Biobank Japan identify 144 novel signals (MAF ≥ 1%), of which 57.0% are replicated in UK Biobank. Additionally, we discover 66 rare (MAF < 1%) variants, 94.4% of them co-incident to common loci, adding to allelic series. Although rare variants have limited contribution to overall trait variance, these lead, in carriers, substantial loss of predictive accuracy from polygenic predictions of disease risk from common variant alone. We capture groups with up to 16-fold variation in type 2 diabetes (T2D) prevalence by integration of genetic risk scores of fasting plasma glucose and T2D and the I349F rare protective variant. This study highlights the need to consider the joint contribution of both common and rare variants on inherited risk of metabolic traits and related diseases. Metabolic traits are heritable intermediate phenotypes widely used in assessing the risk of various diseases. By conducting a genome-wide meta-analysis for metabolic traits in 288,137 East Asians, the authors highlight the interplay of common and rare variants on inherited risk of metabolic traits.
AbstractList Metabolic traits are heritable phenotypes widely-used in assessing the risk of various diseases. We conduct a genome-wide association analysis (GWAS) of nine metabolic traits (including glycemic, lipid, liver enzyme levels) in 125,872 Korean subjects genotyped with the Korea Biobank Array. Following meta-analysis with GWAS from Biobank Japan identify 144 novel signals (MAF ≥ 1%), of which 57.0% are replicated in UK Biobank. Additionally, we discover 66 rare (MAF < 1%) variants, 94.4% of them co-incident to common loci, adding to allelic series. Although rare variants have limited contribution to overall trait variance, these lead, in carriers, substantial loss of predictive accuracy from polygenic predictions of disease risk from common variant alone. We capture groups with up to 16-fold variation in type 2 diabetes (T2D) prevalence by integration of genetic risk scores of fasting plasma glucose and T2D and the I349F rare protective variant. This study highlights the need to consider the joint contribution of both common and rare variants on inherited risk of metabolic traits and related diseases.Metabolic traits are heritable intermediate phenotypes widely used in assessing the risk of various diseases. By conducting a genome-wide meta-analysis for metabolic traits in 288,137 East Asians, the authors highlight the interplay of common and rare variants on inherited risk of metabolic traits.
Metabolic traits are heritable intermediate phenotypes widely used in assessing the risk of various diseases. By conducting a genome-wide meta-analysis for metabolic traits in 288,137 East Asians, the authors highlight the interplay of common and rare variants on inherited risk of metabolic traits.
Metabolic traits are heritable phenotypes widely-used in assessing the risk of various diseases. We conduct a genome-wide association analysis (GWAS) of nine metabolic traits (including glycemic, lipid, liver enzyme levels) in 125,872 Korean subjects genotyped with the Korea Biobank Array. Following meta-analysis with GWAS from Biobank Japan identify 144 novel signals (MAF ≥ 1%), of which 57.0% are replicated in UK Biobank. Additionally, we discover 66 rare (MAF < 1%) variants, 94.4% of them co-incident to common loci, adding to allelic series. Although rare variants have limited contribution to overall trait variance, these lead, in carriers, substantial loss of predictive accuracy from polygenic predictions of disease risk from common variant alone. We capture groups with up to 16-fold variation in type 2 diabetes (T2D) prevalence by integration of genetic risk scores of fasting plasma glucose and T2D and the I349F rare protective variant. This study highlights the need to consider the joint contribution of both common and rare variants on inherited risk of metabolic traits and related diseases.Metabolic traits are heritable phenotypes widely-used in assessing the risk of various diseases. We conduct a genome-wide association analysis (GWAS) of nine metabolic traits (including glycemic, lipid, liver enzyme levels) in 125,872 Korean subjects genotyped with the Korea Biobank Array. Following meta-analysis with GWAS from Biobank Japan identify 144 novel signals (MAF ≥ 1%), of which 57.0% are replicated in UK Biobank. Additionally, we discover 66 rare (MAF < 1%) variants, 94.4% of them co-incident to common loci, adding to allelic series. Although rare variants have limited contribution to overall trait variance, these lead, in carriers, substantial loss of predictive accuracy from polygenic predictions of disease risk from common variant alone. We capture groups with up to 16-fold variation in type 2 diabetes (T2D) prevalence by integration of genetic risk scores of fasting plasma glucose and T2D and the I349F rare protective variant. This study highlights the need to consider the joint contribution of both common and rare variants on inherited risk of metabolic traits and related diseases.
Metabolic traits are heritable phenotypes widely-used in assessing the risk of various diseases. We conduct a genome-wide association analysis (GWAS) of nine metabolic traits (including glycemic, lipid, liver enzyme levels) in 125,872 Korean subjects genotyped with the Korea Biobank Array. Following meta-analysis with GWAS from Biobank Japan identify 144 novel signals (MAF ≥ 1%), of which 57.0% are replicated in UK Biobank. Additionally, we discover 66 rare (MAF < 1%) variants, 94.4% of them co-incident to common loci, adding to allelic series. Although rare variants have limited contribution to overall trait variance, these lead, in carriers, substantial loss of predictive accuracy from polygenic predictions of disease risk from common variant alone. We capture groups with up to 16-fold variation in type 2 diabetes (T2D) prevalence by integration of genetic risk scores of fasting plasma glucose and T2D and the I349F rare protective variant. This study highlights the need to consider the joint contribution of both common and rare variants on inherited risk of metabolic traits and related diseases.
Metabolic traits are heritable phenotypes widely-used in assessing the risk of various diseases. We conduct a genome-wide association analysis (GWAS) of nine metabolic traits (including glycemic, lipid, liver enzyme levels) in 125,872 Korean subjects genotyped with the Korea Biobank Array. Following meta-analysis with GWAS from Biobank Japan identify 144 novel signals (MAF ≥ 1%), of which 57.0% are replicated in UK Biobank. Additionally, we discover 66 rare (MAF < 1%) variants, 94.4% of them co-incident to common loci, adding to allelic series. Although rare variants have limited contribution to overall trait variance, these lead, in carriers, substantial loss of predictive accuracy from polygenic predictions of disease risk from common variant alone. We capture groups with up to 16-fold variation in type 2 diabetes (T2D) prevalence by integration of genetic risk scores of fasting plasma glucose and T2D and the I349F rare protective variant. This study highlights the need to consider the joint contribution of both common and rare variants on inherited risk of metabolic traits and related diseases. Metabolic traits are heritable intermediate phenotypes widely used in assessing the risk of various diseases. By conducting a genome-wide meta-analysis for metabolic traits in 288,137 East Asians, the authors highlight the interplay of common and rare variants on inherited risk of metabolic traits.
ArticleNumber 6642
Author Kim, Bong-Jo
Hwang, Mi Yeong
Kim, Sung Min
Han, Sohee
Park, Hyun-Young
Kim, Young Jin
Yoon, Kyungheon
Lee, Jong-Eun
Cho, Yoon Shin
McCarthy, Mark I.
Moon, Sanghoon
Jang, Hye-Mi
Mahajan, Anubha
Kong, Jinhwa
Shin, Dong Mun
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/36333282$$D View this record in MEDLINE/PubMed
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  publication-title: Nat. Commun.
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Snippet Metabolic traits are heritable phenotypes widely-used in assessing the risk of various diseases. We conduct a genome-wide association analysis (GWAS) of nine...
Metabolic traits are heritable intermediate phenotypes widely used in assessing the risk of various diseases. By conducting a genome-wide meta-analysis for...
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SubjectTerms 45
45/23
45/43
49
49/61
631/208/205/2138
631/208/457/649/2219
692/53
692/699/2743
Asian People - genetics
Association analysis
Biobanks
Blood Glucose - genetics
Diabetes mellitus (non-insulin dependent)
Diabetes Mellitus, Type 2 - genetics
Genetic diversity
Genetic Predisposition to Disease
Genetic variance
Genetic Variation
Genome-Wide Association Study
Genomes
Health risk assessment
Health risks
Humanities and Social Sciences
Humans
Lipids
Meta-analysis
Metabolism
multidisciplinary
Phenotype
Phenotypes
Polygenic inheritance
Polymorphism, Single Nucleotide
Predictions
Risk assessment
Science
Science (multidisciplinary)
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Title The contribution of common and rare genetic variants to variation in metabolic traits in 288,137 East Asians
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