FTO genotype is associated with phenotypic variability of body mass index

There is evidence across several species for genetic control of phenotypic variation of complex traits1, 2, 3, 4, such that the variance among phenotypes is genotype dependent. Understanding genetic control of variability is important in evolutionary biology, agricultural selection programmes and human medicine, yet for complex traits, no individual genetic variants associated with variance, as opposed to the mean, have been identified. Here we perform a meta-analysis of genome-wide association studies of phenotypic variation using ~170,000 samples on height and body mass index (BMI) in human populations. We report evidence that the single nucleotide polymorphism (SNP) rs7202116 at the FTO gene locus, which is known to be associated with obesity (as measured by mean BMI for each rs7202116 genotype)5, 6, 7, is also associated with phenotypic variability. We show that the results are not due to scale effects or other artefacts, and find no other experiment-wise significant evidence for effects on variability, either at loci other than FTO for BMI or at any locus for height. The difference in variance for BMI among individuals with opposite homozygous genotypes at the FTO locus is approximately 7%, corresponding to a difference of ~0.5 kilograms in the standard deviation of weight. Our results indicate that genetic variants can be discovered that are associated with variability, and that between-person variability in obesity can partly be explained by the genotype at the FTO locus. The results are consistent with reported FTO by environment interactions for BMI8, possibly mediated by DNA methylation9, 10. Our BMI results for other SNPs and our height results for all SNPs suggest that most genetic variants, including those that influence mean height or mean BMI, are not associated with phenotypic variance, or that their effects on variability are too small to detect even with samples sizes greater than 100,000.

Portrait of Jacques Offenbach Portraits Men

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Albert Einstein with Robert Andrews Millikan, Albert Michelson and unidentified men; Pasadena, California Portraits Groups; Men

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Therese Godshaw's nee Molling 70th birthday party at the Krakauer home; Boston Portraits Family

Left to right behind table: John Krakauer, Donald, Michael and Robert Godshaw (Children of Hal and Anne), Grandma Therese Godshaw nee Molling, Julius Pick (Grandfather of Robert, Michael and Donald). In front of table: Wendy and Gerry Godshaw (children of Kurt and Edith.

Outdoor family portrait after the memorial services for Therese Godshaw nee Molling at Hal Godshaws house; Argonne Drive, Kenmore, New York.

Front row from left to right: Robert Godshaw, Wendy Godshaw, Rosel Pick (Anne Godshaw's mother), Debbie Godshaw born Mariner, Hal Godshaaw, Francis Schlosstein; 2nd row from left to right: David Dysert, Mickey Sloan born McMath, Edith Godshaw nee Osterer, baby (probably Gary Godshaw), Anne Godshaw born Pick, Julius Pick (Anne's father), Ursula Schlosstein born Gottschalk, Elizabeth Krakauer nee Gottschalk, Michael Godshaw; back row from left to right: Charlie Sloan, Gerald Godshaw (partially hidden), unknown, Kurt Godshaw, John Krakauer, Donald Godshaw, Tom Krakauer, Ralph Schlosstein, John Schlosstein.

Portrait of Elly Goldschmidt and her children Ilse and Robert. Portraits Family

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Ilse and Robert Goldschmidt with their parents Albert Goldschmidt and Elly nee Schoenbeck grandfather Albert Schoenbeck and great grandmother Sophie Schoenbeck nee Mahler. Portraits Family

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Portrait of the engineer and geneologist Robert Goldschmidt Portraits Men

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Members of the Godshaw (Gottschalk) family, Anne, Donald, Molly, Freddy, Jan and Hal; Hannover, Germany. Portraits Family

The family was in Hannover, Germany, for the dedication of the memorial to the Holocaust, the Mahnmal am Opernplatz; from left to right: Anne Godshaw nee Pick, Donald Godshaw, Molly Godshaw nee Peck, Freddy Godshaw, Jan Godshaw nee McKay, and Hal (Hans Ludwig Gottschalk) Godshaw.

Philipp-Coppel Family 1781-1908

Photocopy of family history (Chronik) of Philipp and Coppel family.

heilbrunn frits; heibrunn anne; new york Portraits Couples

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heilbrunn fritz; heilbrunn anne new york Portraits Couples

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heilbrunn fritz; heilbrunn anne; new york Portraits Couples

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heilbrunn fritz; heilbrunn anne; new york portraits couples

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