Genetic and environmental influences on serum lipids and the effects of puberty: a Chinese twin study

Dyslipidemia represents a strong and independent risk factor for cardiovascular disease. Plasma cholesterol, such as total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C), is the common indicator of diagnosing dyslipidemia. Here based on 382 Chinese twin pairs, we explored the magnitude of genetic impact on TC, HDL-C, LDL-C variation and further searched for genetic susceptibility loci for them using genome-wide association study (GWAS). The ACE model was the best fit model with additive genetic parameter (A) accounting for 26.6%, common or shared environmental parameter (C) accounting for 47.8%, unique/non-shared environmental parameter (E) accounting for 25.6% for the variance in HDL-C. The AE model was the best fit model for TC (A: 61.4%; E: 38.6%) and LDL-C (A: 65.5%; E: 34.5%). While no SNPs reached the genome-wide significance level (P < 5 × 10−8), 8, 14, 9 SNPs exceeded the suggestive significance level (P < 1 × 10−5) for TC, HDL-C, LDL-C, respectively. The promising genetic regions for TC, HDL-C, LDL-C were on chromosome 11 around rs7107698, chromosome 5 around rs12518218, chromosome 2 around rs10490120, respectively. Gene-based analysis found 1038, 1033 and 1090 genes nominally associated with TC, HDL-C, LDL-C (P < 0.05), especially FAF1, KLKB1 for TC, KLKB1 for HDL-C, and NTRK1, FAF1, SNTB2 for LDL-C, respectively. The number of common related genes among TC, HDL-C and LDL-C was 71, including FAF1, KLKB1, etc. Pathway enrichment analysis discovered known related pathways-zinc transporters, metal ion SLC transporters for TC, cell adhesion molecules CAMs, IL-6 signaling for HDL, FC epsilon RI signaling pathway, NFAT pathway for LDL, respectively. In conclusion, the TC and LDL-C level is moderately heritable and the HDL-C level is lowly heritable in Chinese population. The genomic loci, functional genes and pathways are identified to account for the heritability of plasma cholesterol level. Our findings provide important insights into plasma cholesterol molecular physiology and expect future research to replicate and validate our results.

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“…HDL-C level is close to some other twin studies ( 11 , 14 , 27 , 48 , 49 ). LDL-C level is similar to the others ( 27 , 42 , 43 , 45 , 47 , 50 ).…”

Section: Discussionsupporting

confidence: 86%

Heritability and Genome-Wide Association Study of Plasma Cholesterol in Chinese Adult Twins

et al. 2018

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“…The zygosity of same‐sex twins was determined through DNA analysis (41.0% of all twins) or via questionnaires (39.6% of all twins). In the DNA analysis, the probability that any twin pair was monozygotic (MZ) twins if all of the markers were concordant was 99.6% [Chen et al, ]. In the questionnaire method, an algorithm was used on the basis of the questions concerning twin confusion, which was derived from the twins with known zygosity; this method yielded a prediction accuracy of 89.2% [Gao et al, ].…”

Section: Methodsmentioning

confidence: 99%

Genetic and environmental influences on the relationship between ADHD symptoms and internalizing problems: A Chinese twin study

Chen

Wang

et al. 2015

American J of Med Genetics Pt B

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Several twin studies have investigated the overlap between attention deficit hyperactivity disorder (ADHD) and externalizing problems; however, limited information is known regarding the genetic and environmental contribution to the overlap between ADHD and internalizing problems. This study examined the genetic and environmental influences on the variation in and covariation between ADHD symptoms and internalizing problems by using the Child Behavior Checklist (CBCL). We investigated 1,316 child and adolescent twins, including 780 monozygotic twins and 536 dizygotic twins, aged 6 years to 18 years from the Chinese Child and Adolescent Twin Registry. ADHD symptoms and internalizing problems were quantified through parent rating by using the Attention Problems Scale and other three scales, which include Anxious/Depressed, Withdrawn, and Somatic Complaints of CBCL. Genetic and environmental susceptibilities common to ADHD symptoms and internalizing problems were examined through bivariate twin modeling. Results showed that genetic factors substantially influenced the ADHD symptoms with a heritability of 72%. Modest genetic influences and substantial shared environmental influences (20-77%) were observed in the three internalizing problem scales. Common genetic and shared environmental influences were essential for the overlap between ADHD and the three internalizing problems respectively. Approximately one-fifth of the genetic variance of ADHD symptoms was shared with anxiety/depression. In conclusion, substantial genetic and shared environmental influences on ADHD symptoms and internalizing problems were observed in Chinese children and adolescents. Our finding supports a common etiology between ADHD and internalizing problems. This finding can also help explain the coexistence of these behavior problems.

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“…Lp(a) consist of an LDL-like particle attached to apolipoprotein(a). LPA is the major quantitative trait locus controlling the lipoprotein(a) (Lp(a)) plasma concentrations [9], which are highly heritable in all populations studied so far [1], including Asians [10,11]. Individual Lp(a) levels range from <0.1mg/dl to >200mg/dl.…”

Section: Introductionmentioning

confidence: 99%

Lack of association of rs3798220 with small apolipoprotein(a) isoforms and high lipoprotein(a) levels in East and Southeast Asians

et al. 2015

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Genetic and environmental influences on serum lipids and the effects of puberty: a Chinese twin study

Abstract: Genes and the environment have different effects on the levels of different lipids. The shared environmental effects on lipids are very important in children. The role of puberty on lipids deserves future study.

Cited by 13 publications

References 39 publications

Heritability and Genome-Wide Association Study of Plasma Cholesterol in Chinese Adult Twins

Heritability and Genome-Wide Association Study of Plasma Cholesterol in Chinese Adult Twins

Genetic and environmental influences on the relationship between ADHD symptoms and internalizing problems: A Chinese twin study

Lack of association of rs3798220 with small apolipoprotein(a) isoforms and high lipoprotein(a) levels in East and Southeast Asians

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