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Men and women differ substantially regarding height, weight, and body fat. Interestingly, previous work detecting genetic effects for waist-to-hip ratio, to assess body fat distribution, has found that many of these showed sex-differences. However, systematic searches for sex-differences in genetic effects have not yet been conducted. Therefore, we undertook a genome-wide search for sexually dimorphic genetic effects for anthropometric traits including 133,723 individuals in a large meta-analysis and followed promising variants in further 137,052 individuals, including a total of 94 studies. We identified seven loci with significant sex-difference including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were significant in women, but not in men. Of interest is that sex-difference was only observed for waist phenotypes, but not for height or body-mass-index. We found no evidence for sex-differences with opposite effect direction for men and women. The PPARG locus is of specific interest due to its link to diabetes genetics and therapy. Our findings demonstrate the importance of investigating sex differences, which may lead to a better understanding of disease mechanisms with a potential relevance to treatment options.
Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behavior. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9,784 bipolar disorder patients and 30,471 controls, the largest GWAS of BD to date. In this study, to increase power we used ~2,000 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the Xchromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, p = 5.87×10-9; odds ratio = 1.12) and markers within ERBB2 (rs2517959, p = 4.53×10-9; odds ratio = 1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS.
HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders
(2021)
Bipolar affective disorder (BD) is a severe psychiatric illness, for which lithium (Li) is the gold standard for acute and maintenance therapies. The therapeutic response to Li in BD is heterogeneous and reliable biomarkers allowing patients stratification are still needed. A GWAS performed by the International Consortium on Lithium Genetics (ConLiGen) has recently identified genetic markers associated with treatment responses to Li in the human leukocyte antigens (HLA) region. To better understand the molecular mechanisms underlying this association, we have genetically imputed the classical alleles of the HLA region in the European patients of the ConLiGen cohort. We found our best signal for amino-acid variants belonging to the HLA-DRB1*11:01 classical allele, associated with a better response to Li (p < 1 × 10−3; FDR < 0.09 in the recessive model). Alanine or Leucine at position 74 of the HLA-DRB1 heavy chain was associated with a good response while Arginine or Glutamic acid with a poor response. As these variants have been implicated in common inflammatory/autoimmune processes, our findings strongly suggest that HLA-mediated low inflammatory background may contribute to the efficient response to Li in BD patients, while an inflammatory status overriding Li anti-inflammatory properties would favor a weak response.
A study was undertaken of the floristic patterns in coastal rainforest (low closed forest) of Shoalwater Bay, central Queensland. The site encompasses 60 km of coastline, extending from latitude 22° 08’ 30’’ to 22° 30’ 0” and longitude 150° 02’ 00” to 150° 24’ 30”. The rainforest grows on coastal Holocene sand dunes, swales and sand flats, distributed as a series of 27 discrete patches greater than one hectare along 60 kilometres of coastline. Mean patch size was 10.7 hectares (maximum 150 hectares). The flora was predominantly woody, and lacked the complex growth forms of Webb (1968). Floristic links with central and north Queensland were strong, with some species distributions extending into Malesia and the Pacific. Three physical strata, emergent (composed of trees), canopy (composed of trees, vines and epiphytes) and sub-canopy (trees, vines and herbs) were recognised. The herb layer was very poorly developed. Eighty-one species were recorded, representing 42 families and 72 genera.
Sixty three quadrats were sampled across the rainforest patches to measure abundance of all vascular taxa using frequency score. Five floristic groups were defined from agglomerative classification analysis, one representing mixed forest, two representing low microphyll vine forest (LMVF) and two representing microphyll vine thicket (MVT). The vegetation at the study site was predominantly MVT. Five species groups were defined, one correlated with the mixed forest, one with the LMVF and one with the MVT. The remaining species groups represented ubiquitous and widespread species. Floristic patterns were found to be strongly influenced by three environmental variables using canonical correspondence analysis. The strongest variable was drainage, which separated the mixed forest from the vine forest/thicket. The LMVF/MVT vegetation forms a continuum along an environmental gradient, influenced by exposure to onshore-winds and landform height. The mesic/protected extreme was represented by the tallest LMVF situated in swales, whilst at the exposure/ elevation extreme was represented by wind-sheared MVT located on foredunes.