Assessing the impact of alcohol consumption on the genetic contribution to mean corpuscular volume

Thompson, Andrew; King, Katharine; Morris, Andrew P.; Pirmohamed, Munir

doi:10.1093/hmg/ddab147

Cited by 3 publications

(2 citation statements)

References 49 publications

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“…We found blood cell vQTLs tagged genes related to diet. Previous GWAS of diet identified loci related to blood lipids 38 and glycated hemoglobin 39 but not to blood cell traits analysed here; however, others have reported that alcohol intake increases mean corpuscular volume independent of the genetic contribution to the level of mean corpuscular volume 40 . In our study, alcohol consumption-related loci significantly overlapped with vQTLs for platelet count, the function of which can be significantly affected by alcohol drinking 41 .…”

Section: Discussioncontrasting

confidence: 61%

Genome-wide analyses of variance in blood cell phenotypes provide new insights into complex trait biology and prediction

Xiang,

Liu,

Ben-Eghan

et al. 2024

Preprint

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Blood cell phenotypes are routinely tested in healthcare to inform clinical decisions. Genetic variants influencing mean blood cell phenotypes have been used to understand disease aetiology and improve prediction; however, additional information may be captured by genetic effects on observed variance. Here, we mapped variance quantitative trait loci (vQTL), i.e. genetic loci associated with trait variance, for 29 blood cell phenotypes from the UK Biobank (N~408,111). We discovered 176 independent blood cell vQTLs, of which 147 were not found by additive QTL mapping. vQTLs displayed on average 1.8-fold stronger negative selection than additive QTL, highlighting that selection acts to reduce extreme blood cell phenotypes. Variance polygenic scores (vPGSs) were constructed to stratify individuals in the INTERVAL cohort (N~40,466), where genetically less variable individuals (low vPGS) had increased conventional PGS accuracy (by ~19%) than genetically more variable individuals. Genetic prediction of blood cell traits improved by ~10% on average combining PGS with vPGS. Using Mendelian randomisation and vPGS association analyses, we found that alcohol consumption significantly increased blood cell trait variances highlighting the utility of blood cell vQTLs and vPGSs to provide novel insight into phenotype aetiology as well as improve prediction.

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Section: Discussioncontrasting

confidence: 61%

Genome-wide analyses of variance in blood cell phenotypes provide new insights into complex trait biology and prediction

Xiang,

Liu,

Ben-Eghan

et al. 2024

Preprint

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“…Overall, four genes ( SCAMP2, SCAMP5, MPI, and FAM219B ) were identified by all four methods, and six of the 165 discovered genes ( FBXO28 , NEIL2 , HAUS4 , IGDCC4 , RP11- 298I3.5 , RP11-298I3.5 ) were not within 1Mb of SNPs identified by prior GWAS of coffee or caffeine traits ( Supplementary Table 11 ; Figure 1B ; Table 2 ). These novel genes have been associated with substance use (e.g., HAUS4 and smoking initiation 73 ), educational outcomes (e.g., HAUS4 and educational attainment 90 ), and biomarkers (e.g., FBXO28 and mean platelet volume 91 ; IGDCC4 and mean corpuscular volume 92 ).…”

Section: Resultsmentioning

confidence: 99%

Genome-Wide Association Studies of Coffee Intake in UK/US Participants of European Ancestry Uncover Gene-Cohort Influences

Thorpe,

Fontanillas,

Pham

et al. 2023

Preprint

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Coffee is one of the most widely consumed beverages. We performed a genome-wide association study (GWAS) of coffee intake in US-based 23andMe participants (N=130,153) and identified 7 significant loci, with many replicating in three multi-ancestral cohorts. We examined genetic correlations and performed a phenome-wide association study across thousands of biomarkers and health and lifestyle traits, then compared our results to the largest available GWAS of coffee intake from UK Biobank (UKB;N=334,659). The results of these two GWAS were highly discrepant. We observed positive genetic correlations between coffee intake and psychiatric illnesses, pain, and gastrointestinal traits in 23andMe that were absent or negative in UKB. Genetic correlations with cognition were negative in 23andMe but positive in UKB. The only consistent observations were positive genetic correlations with substance use and obesity. Our study shows that GWAS in different cohorts could capture cultural differences in the relationship between behavior and genetics.

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Maternal pre-pregnancy BMI, offspring epigenome-wide DNA methylation, and childhood obesity: findings from the Boston Birth Cohort

Si,

Meir,

Hong

et al. 2023

BMC Med

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Background Maternal pre-pregnancy obesity is an established risk factor for childhood obesity. Investigating epigenetic alterations induced by maternal obesity during fetal development could gain mechanistic insight into the developmental origins of childhood obesity. While obesity disproportionately affects underrepresented racial and ethnic mothers and children in the USA, few studies investigated the role of prenatal epigenetic programming in intergenerational obesity of these high-risk populations. Methods This study included 903 mother–child pairs from the Boston Birth Cohort, a predominantly urban, low-income minority birth cohort. Mother-infant dyads were enrolled at birth and the children were followed prospectively to age 18 years. Infinium Methylation EPIC BeadChip was used to measure epigenome-wide methylation level of cord blood. We performed an epigenome-wide association study of maternal pre-pregnancy body mass index (BMI) and cord blood DNA methylation (DNAm). To quantify the degree to which cord blood DNAm mediates the maternal BMI-childhood obesity, we further investigated whether maternal BMI-associated DNAm sites impact birthweight or childhood overweight or obesity (OWO) from age 1 to age 18 and performed corresponding mediation analyses. Results The study sample contained 52.8% maternal pre-pregnancy OWO and 63.2% offspring OWO at age 1–18 years. Maternal BMI was associated with cord blood DNAm at 8 CpG sites (genome-wide false discovery rate [FDR] < 0.05). After accounting for the possible interplay of maternal BMI and smoking, 481 CpG sites were discovered for association with maternal BMI. Among them 123 CpGs were associated with childhood OWO, ranging from 42% decrease to 87% increase in OWO risk for each SD increase in DNAm. A total of 14 identified CpG sites showed a significant mediation effect on the maternal BMI-child OWO association (FDR < 0.05), with mediating proportion ranging from 3.99% to 25.21%. Several of these 14 CpGs were mapped to genes in association with energy balance and metabolism (AKAP7) and adulthood metabolic syndrome (CAMK2B). Conclusions This prospective birth cohort study in a high-risk yet understudied US population found that maternal pre-pregnancy OWO significantly altered DNAm in newborn cord blood and provided suggestive evidence of epigenetic involvement in the intergenerational risk of obesity.

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Assessing the impact of alcohol consumption on the genetic contribution to mean corpuscular volume

Cited by 3 publications

References 49 publications

Genome-wide analyses of variance in blood cell phenotypes provide new insights into complex trait biology and prediction

Genome-wide analyses of variance in blood cell phenotypes provide new insights into complex trait biology and prediction

Genome-Wide Association Studies of Coffee Intake in UK/US Participants of European Ancestry Uncover Gene-Cohort Influences

Maternal pre-pregnancy BMI, offspring epigenome-wide DNA methylation, and childhood obesity: findings from the Boston Birth Cohort

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