Genome-wide association analysis of metabolic traits in a birth cohort from a founder population

Sabatti, Chiara; Service, Susan; Hartikainen, Anna-Liisa; Pouta, Anneli; Ripatti, Samuli; Brodsky, Jae; Jones, Chris G; Zaitlen, Noah; Varilo, Teppo; Kaakinen, Marika; Sovio, Ulla; Ruokonen, Aimo; Laitinen, Jaana; Jakkula, Eveliina; Coin, Lachlan; Hoggart, Clive; Collins, Andrew; Turunen, Hannu; Gabriel, Stacey; Elliot, Paul; McCarthy, Mark I.; Daly, Mark J.; Järvelin, Marjo‐Riitta; Freimer, Nelson B.; Peltonen, Leena

doi:10.1038/ng.271

Cited by 681 publications

(729 citation statements)

References 49 publications

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“…In previous studies this candidate gene has been found to explain approximately 1% of the variation of BMI in several adult populations. [36][37][38] This gene was found to be associated with BMI from 7 years of age onwards in the UK twin sample 15 and a similar finding was also observed in Danish children. 39 However, the FTO gene was able to explain only a small proportion of the genetic variation of BMI in the UK study.…”

Section: International Journal Of Obesitysupporting

confidence: 66%

“…Thus, part of the genetic effect found in the previous studies may be mixed with environmental factors. These findings, when found more widely, would help reconcile why the very large genome-wide studies are unable to account for more than about 1% of the variance in BMI, [36][37][38] whereas family studies find evidence for substantial heritability even when common environmental effects are allowed for.…”

Section: Possible Sources Of Bias In Adoption Studiesmentioning

confidence: 88%

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The genetic and environmental influences on childhood obesity: a systematic review of twin and adoption studies

et al. 2009

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In this systematic review, we aimed to collect together all previous twin and adoption studies on childhood and adolescent obesity up to the age of 18 years. Using several sources, we identified nine twin and five adoption studies; all of these studies had used relative weight as an indicator of obesity. Except the two twin studies from the Korean population, all studies represented Caucasian populations. In a meta-analysis of these twin studies, we found that genetic factors had a strong effect on the variation of body mass index (BMI) at all ages. The common environmental factors showed a substantial effect in mid-childhood, but this effect disappeared at adolescence. Adoption studies supported the role of family environment in childhood obesity as correlations were found between adoptees and adoptive parents; however, correlations were substantially stronger between parents and their biological offspring, further supporting the importance of genetic factors. In the future, more studies implementing genetic and environmental measures into twin models are needed as they allow estimation of the proportion of total genetic variation explained by candidate genes and analyses of gene-environment interactions. More studies of genetic architecture in non-Caucasian populations, of gene-environment interactions, and of body composition and body fat distribution are needed. IntroductionChildhood obesity is one of the major public health problems in the modern world. In the period [2003][2004][2005][2006], 32% of the US children were classified as obese or overweight, 1 and increasing trends in childhood obesity are seen all over the world. 2 These results are especially alarming as overweight children show a high risk of becoming obese adults. 3,4 Childhood is an important period of life for health interventions as health-related behaviors are just in formation, and it seems possible to intervene for preventing the development of obesity. 5 Thus, it is crucial to further understand the background mechanisms of childhood obesity to find even more effective measures to prevent it before it begins to produce more or less irreversible health damages.Both genetic and environmental factors will probably contribute to childhood obesity. 6 Family studies have shown that obesity runs in families, although more detailed twin, adoption and family studies have shown that genetic differences between individuals explain a major proportion of the within-population variation in body mass index (BMI, kg m À2 ) in adulthood. [7][8][9] It is probable that genetic factors have an important role in childhood obesity also, but their role may be different or they may result from other genes than those that operate in adulthood. 10 The environmental factors shared by family members, such as co-twins in twin studies, have shown only a slight effect on the variation of adult BMI. 7,8 However, they may have a more important role in childhood, where parents and their offspring live together and where siblings obviously have a much greater opportu...

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Section: International Journal Of Obesitysupporting

confidence: 66%

Section: Possible Sources Of Bias In Adoption Studiesmentioning

confidence: 88%

The genetic and environmental influences on childhood obesity: a systematic review of twin and adoption studies

et al. 2009

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“…[15][16][17][18][19][20][21][22][23] As these studies have a cross-sectional design, it is not possible to examine the effect of a SNP on development of a trait. We suggest that rs1042522 has a role in the development of DBP and waist circumference during ageing and therefore, a SNP effect alone will be less informative compared with a SNP*time interaction in this case.…”

Section: Discussionmentioning

confidence: 99%

Codon 72 polymorphism (rs1042522) of TP53 is associated with changes in diastolic blood pressure over time

et al. 2011

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p53 is involved in stress response, metabolism and cardiovascular functioning. The C-allele of rs1042522 in the gene encoding for p53 is associated with longevity and cancer. In this study, we aimed to investigate the association of rs1042522 with changes in blood pressure, BMI and waist circumference using a longitudinal approach. Rs1042522 was analyzed in two longitudinal studies; the Doetinchem Cohort Study (DCS) and the Botnia Prospective Study (BPS). Changes in quantitative traits over time were investigated according to rs1042522 genotypes. An association between rs1042522 and changes in diastolic blood pressure (DBP) in the DCS over time was observed (P¼0.004). Furthermore, a borderline significant association was detected with changes in waist circumference over time (P¼0.03). These findings were also observed in the BPS (P¼0.02 and P¼0.05). The C/C-genotype (Pro/Pro) showed the most moderate time-related increase for the studied endpoints. Furthermore, data from the BPS suggested that the C/C-genotype protects against increases in glucose levels over time at 30 and 60 min during oral glucose tolerance test (P¼0.01 and P¼0.02). In conclusion, we found an association between the C/C-genotype of rs1042522 and changes in DBP and waist circumference over time. This might contribute to the longevity phenotype observed for the same genotype by others.

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“…A number of genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) in the chromosome 6 region that includes ELOVL2 to be strongly associated with plasma fatty acid proportions (Aulchenko et al 2009;Sabatti et al 2009;Tanaka et al 2009;Illig et al 2010). A subsequent meta-analysis confirmed a number of minor allele associations with higher EPA and DPA and lower DHA proportions (Lemaitre et al 2011).…”

Section: Introductionmentioning

confidence: 99%

ELOVL2 gene polymorphisms are associated with increases in plasma eicosapentaenoic and docosahexaenoic acid proportions after fish oil supplement

et al. 2013

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Fish oil supplementation provides an inconsistent degree of protection from cardiovascular disease (CVD), which may be attributed to genetic variation. Single nucleotide polymorphisms (SNPs) in the elongation-ofvery-long-chain-fatty-acids-2 (ELOVL2) gene have been strongly associated with plasma proportions of n-3 longchain polyunsaturated fatty acids (LC-PUFA). We investigated the effect of genotype interaction with fish oil dosage on plasma n-3 LC-PUFA proportions in a parallel doubleblind controlled trial, involving 367 subjects randomised to treatment with 0.45, 0.9 and 1.8 g/day eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (1.51:1) or olive oil placebo for 6 months. We genotyped 310 subjects for ELOVL2 gene SNPs rs3734398, rs2236212 and rs953413. At baseline, carriers of all minor alleles had lower proportions of plasma DHA than non-carriers (P = 0.021-0.030). Interaction between genotype and treatment was a significant determinant of plasma EPA (P \ 0.0001) and DHA (P = 0.004-0.032). After the 1.8 g/day dose, carriers of ELOVL2 SNP minor alleles had approximately 30 % higher proportions of EPA (P = 0.002-0.004) and 9 % higher DHA (P = 0.013-0.017) than non-carriers. Minor allele carriers could therefore particularly benefit from a high intake of EPA and DHA in maintaining high levels of plasma n-3 PUFA conducive to protection from CVD.

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Genome-wide association analysis of metabolic traits in a birth cohort from a founder population

Cited by 681 publications

References 49 publications

The genetic and environmental influences on childhood obesity: a systematic review of twin and adoption studies

The genetic and environmental influences on childhood obesity: a systematic review of twin and adoption studies

Codon 72 polymorphism (rs1042522) of TP53 is associated with changes in diastolic blood pressure over time

ELOVL2 gene polymorphisms are associated with increases in plasma eicosapentaenoic and docosahexaenoic acid proportions after fish oil supplement

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