Manon Bernard

Publications (6)35.89 Total impact

• Article: FTO, obesity and the adolescent brain.

  Melkaye G Melka, Jesse Gillis, Manon Bernard, Michal Abrahamowicz, M Mallar Chakravarty, Gabriel T Leonard, Michel Perron, Louis Richer, Suzanne Veillette, Tobias Banaschewski, [......], Andreas Ströhle, Jürgen Gallinat, Maren Struve, Eva Lattka, Melanie Waldenberger, Gunter Schumann, Paul Pavlidis, Daniel Gaudet, Tomás Paus, Zdenka Pausova
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  ABSTRACT: Genetic variations in FTO, a well-replicated gene locus of obesity, appear to be associated also with reduced regional brain volumes in elderly. Here, we examined whether FTO is associated with total brain-volume in adolescence, thus exploring possible developmental effects of FTO. We studied a population-based sample of 598 adolescents recruited from the French-Canadian founder population in whom we measured brain volume by magnetic resonance imaging. Total fat mass was assessed with bioimpedance and body mass index was determined with anthropometry. Genotype-phenotype associations were tested with Merlin under an additive model. We found that the G allele of fto (rs9930333) was associated with higher total body fat (p=0.002) and lower brain volume (p=0.005). The same allele was also associated with higher lean body mass (p=0.03) and no difference in height (p=0.99). Principal component analysis identified a shared inverse variance between the brain volume and total body fat, which was associated with FTO at p=5.5x10(-6). These results were replicated in two independent samples of 413 and 718 adolescents; in a meta-analysis of all three samples (n=1,729 adolescents), FTO was associated with this shared inverse variance at p=1.3x10(-9). Co-expression networks analysis supported the possibility that the underlying FTO effects may occur during embryogenesis. In conclusion, FTO is associated with shared inverse variance between body adiposity and brain volume, suggesting that this gene may exert inverse effects on adipose and brain tissues. Given the completion of the overall brain growth in early childhood, these effects may have their origins during early development.
  Human Molecular Genetics 11/2012; · 7.64 Impact Factor
• Article: Genome-wide scan for loci of adolescent obesity and their relationship with blood pressure.

  Melkaye G Melka, Manon Bernard, Amel Mahboubi, Michal Abrahamowicz, Andrew D Paterson, Catriona Syme, Anbarasu Lourdusamy, Gunter Schumann, Gabriel T Leonard, Michel Perron, Louis Richer, Suzanne Veillette, Daniel Gaudet, Tomas Paus, Zdenka Pausova
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  ABSTRACT: Hypertension, typically considered a disorder of adulthood, is now emerging in adolescence. This is mainly due to the growing prevalence of obesity and the fact that excess body fat increases blood pressure (BP). The objective of the study was to investigate whether genome-wide identified gene loci of obesity are associated with elevated BP in adolescence. This was a genotype-phenotype association study. The study was conducted in a French-Canadian founder population. Participants included 598 adolescents, aged 12-18 yr. Testing associations between 530,011 single-nucleotide polymorphisms (SNP; Human610W-Quad BeadChip) and obesity measures and between identified SNP and BP. Total fat mass (TFM) was assessed with bioelectrical impedance, and body mass index (BMI) was determined with anthropometry. BP was measured beat by beat during an hour-long protocol. The genome-wide association studies of TFM and BMI revealed two novel and several previously identified loci of obesity. The former were PAX5 (rs16933812, TFM: P = 9.3 × 10(-9)) and MRPS22 (rs7638110, BMI: P = 4.6 × 10(-8)), and the top ones among the latter (P < 5 × 10(-4)) were MC4R (rs17773430, BMI: P = 5.8 × 10(-6)), FTO (rs9930333, BMI: P = 1.9 × 10(-4)), and MTCH2 (rs7120548, BMI: P = 1.9 × 10(-4)). From these five, only the PAX5, MRPS22, and FTO were also associated with BP; their minor allele homozygotes vs. major allele homozygotes showed greater TFM by 2.9-8.0 kg and higher BP by 3.3-6.7 mm Hg. Genome-wide association studies conducted in an adolescent founder population revealed two new and a number of previously identified loci of obesity and demonstrated that several but not all of these loci are also associated with elevated BP. These results begin to reveal the genetic architecture of obesity-induced hypertension.
  The Journal of clinical endocrinology and metabolism 01/2012; 97(1):E145-50. · 6.50 Impact Factor
• Article: KCTD8 Gene and Brain Growth in Adverse Intrauterine Environment: A Genome-wide Association Study.

  Tomás Paus, Manon Bernard, M Mallar Chakravarty, George Davey Smith, Jesse Gillis, Anbarasu Lourdusamy, Melkaye G Melka, Gabriel Leonard, Paul Pavlidis, Michel Perron, G Bruce Pike, Louis Richer, Gunter Schumann, Nicholas Timpson, Roberto Toro, Suzanne Veillette, Zdenka Pausova
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  ABSTRACT: The most dramatic growth of the human brain occurs in utero and during the first 2 years of postnatal life. Genesis of the cerebral cortex involves cell proliferation, migration, and apoptosis, all of which may be influenced by prenatal environment. Here, we show that variation in KCTD8 (potassium channel tetramerization domain 8) is associated with brain size in female adolescents (rs716890, P = 5.40 × 10(-09)). Furthermore, we found that the KCTD8 locus interacts with prenatal exposure to maternal cigarette smoking vis-à-vis cortical area and cortical folding: In exposed girls only, the KCTD8 locus explains up to 21% of variance. Using head circumference as a proxy of brain size at 7 years of age, we have replicated this gene-environment interaction in an independent sample. We speculate that KCTD8 might modulate adverse effects of smoking during pregnancy on brain development via apoptosis triggered by low intracellular levels of potassium, possibly reducing the number of progenitor cells.
  Cerebral Cortex 12/2011; 22(11):2634-42. · 6.54 Impact Factor
• Article: Genes, maternal smoking, and the offspring brain and body during adolescence: design of the Saguenay Youth Study.

  Zdenka Pausova, Tomás Paus, Michal Abrahamowicz, Jason Almerigi, Nadine Arbour, Manon Bernard, Daniel Gaudet, Petr Hanzalek, Pavel Hamet, Alan C Evans, [......], Michel Perron, Bruce Pike, Alain Pitiot, Louis Richer, Jean R Séguin, Catriona Syme, Roberto Toro, Richard E Tremblay, Suzanne Veillette, Kate Watkins
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  ABSTRACT: The search for genes of complex traits is aided by the availability of multiple quantitative phenotypes collected in geographically isolated populations. Here we provide rationale for a large-scale study of gene-environment interactions influencing brain and behavior and cardiovascular and metabolic health in adolescence, namely the Saguenay Youth Study (SYS). The SYS is a retrospective study of long-term consequences of prenatal exposure to maternal cigarette smoking (PEMCS) in which multiple quantitative phenotypes are acquired over five sessions (telephone interview, home, hospital, laboratory, and school). To facilitate the search for genes that modify an individual's response to an in utero environment (i.e. PEMCS), the study is family-based (adolescent sibships) and is carried out in a relatively geographically isolated population of the Saguenay Lac-Saint-Jean (SLSJ) region in Quebec, Canada. DNA is acquired in both biological parents and in adolescent siblings. A genome-wide scan will be carried out with sib-pair linkage analyses, and fine mapping of identified loci will be done with family-based association analyses. Adolescent sibships (12-18 years of age; two or more siblings per family) are recruited in high schools throughout the SLSJ region; only children of French-Canadian origin are included. Based on a telephone interview, potential participants are classified as exposed or nonexposed prenatally to maternal cigarette smoking; the two groups are matched for the level of maternal education and the attended school. A total of 500 adolescent participants in each group will be recruited and phenotyped. The following types of datasets are collected in all adolescent participants: (1) magnetic resonance images of brain, abdominal fat, and kidneys, (2) standardized and computer-based neuropsychological tests, (3) hospital-based cardiovascular, body-composition and metabolic assessments, and (4) questionnaire-derived measures (e.g. life habits such as eating and physical activity; drug, alcohol use and delinquency; psychiatric symptoms; personality; home and school environment; academic and vocational attitudes). Parents complete a medical questionnaire, home-environment questionnaire, a handedness questionnaire, and a questionnaire about their current alcohol and drug use, depression, anxiety, and current and past antisocial behavior. To date, we have fully phenotyped a total of 408 adolescent participants. Here we provide the description of the SYS and, using the initial sample, we present information on ascertainment, demographics of the exposed and nonexposed adolescents and their parents, and the initial MRI-based assessment of familiality in the brain size and the volumes of grey and white matter.
  Human Brain Mapping 07/2007; 28(6):502-18. · 5.88 Impact Factor
• Article: Genome-wide scan for linkage to obesity-associated hypertension in French Canadians.

  Zdenka Pausova, Daniel Gaudet, Francis Gossard, Manon Bernard, Mary L Kaldunski, Michele Jomphe, Johanne Tremblay, Thomas J Hudson, Gerard Bouchard, Theodore A Kotchen, Allen W Cowley, Pavel Hamet
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  ABSTRACT: Essential hypertension is a heterogeneous disorder that is thought to develop because of several overlapping subsets of underlying mechanisms. One such causal pathway may involve pathophysiological alterations induced by obesity. In the present study, we examined whether investigating clinically defined subtypes of hypertension, such as obesity-associated hypertension, facilitates the search for its genes. Fifty-five extended families were selected on the basis of having > or =2 siblings affected by hypertension from a geographically remote French-Canadian population. Fifteen of these families showed a high prevalence (> or =70%) of obesity. Genome-wide scan using qualitative multipoint linkage analysis (GeneHunter 2.1; marker density <10 cM) was performed in the entire set of hypertensive families and the subset with high prevalence of obesity. In the scan involving all 55 families, the most significant loci (logarithm of odds [LOD] score=2.5) were identified on chromosomes 1 (D1S1597) and 11 (D11S1999). In the scan including only the subset of families with obesity-hypertension, the most significant locus (LOD score=3.1) was found on chromosome 1 in the same region as the scan involving all families (D1S1597). Genotyping additional markers increased the significance of this locus (LOD score=3.5) and refined its position (D1S2672). Several candidate genes of obesity-hypertension are located in close proximity; these include the tumor necrosis factor receptor 2 and atrial natriuretic peptide genes. These results suggest that investigating clinically defined subtypes of hypertension, such as obesity-associated hypertension, may facilitate the search for genes of this complex disorder.
  Hypertension 01/2006; 46(6):1280-5. · 6.21 Impact Factor
• Article: Procedure to protect confidentiality of familial data in community genetics and genomic research

  Daniel Gaudet, Steve Arsenault, Céline Bélanger, Thomas Hudson, Patrice Perron, Manon Bernard, Pavel Hamet
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  ABSTRACT: The collection of familial data is an essential step for community genetics programs or genetic research. Ethical issues concerning privacy and confidentiality present a major challenge in such programs. In order to keep familial data confidential, we have developed a family-based numerical coding procedure which allows the use of confidential data and the determination of familial relationships without risk of disclosure. This procedure is composed of two parts: the physical separation of identifying information and individual data; and the use of a code containing all the information required to build family trees. This procedure has been used in Eastern Quebec since 1995, mainly for screening, genetic counseling, research on familial dyslipidemias, public health intervention, and research projects on the genetics of complex traits, such as arterial hypertension and coronary artery disease.
  Clinical Genetics 12/2001; 55(4):259 - 264. · 3.13 Impact Factor